Hypertension, Prehypertension
Conditions
Brief summary
The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo.
Detailed description
1. The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo. 2. The investigators further hypothesize that reducing ET-1 vasoconstrictor activity contributes to the improvement in endothelial vasodilator function associated with nebivolol.
Interventions
DRUGNebivolol
5 mg tablet to be taken by mouth once per day for 12 weeks
DRUGMetoprolol
100 mg tablet to be taken by mouth once per day for 12 weeks
DRUGPlacebo
gelatin capsule to be taken by mouth once per day for 12 weeks
OTHERForearm Blood Flow (FBF) response to BQ-123 (100 mol/min)
The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks.
OTHERFBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min)
The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.
OTHERFBF response to Acetylcholine
The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.
OTHERFBF response to Sodium Nitroprusside
The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.
OTHERFBF response to BQ-123+BQ-788+ACh
The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.
Sponsors
Forest Laboratories
University of Colorado, Boulder
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be men and women of all races and ethnic backgrounds aged 45-65 years. * Subjects will be prehypertensive/hypertensive defined as resting systolic blood pressure \>130 mmHg and \< 160 mm Hg and/or diastolic blood pressure \>80 mmHg and \< 100 mm Hg. * All of the women in the study will be postmenopausal (at least 1 year from last menstrual cycle) and not receiving hormone replacement therapy (HRT) currently or in the preceding 3-year period. * Lastly, candidates will be sedentary as determined from the Stanford Physical Activity Questionnaire (\<35 kcal/wk) and will not have engaged in any program of regular physical activity for at least 1 year prior to the study.
Exclusion criteria
* Candidates who smoke (currently or in the past 7 years), report more than low-risk alcohol consumption as defined as no more than 14 standard drinks/wk and no more than 4 standard drinks/day for men and 7 standard drinks/wk and 3 standard drinks/day for women (a standard drink is defined as 12 ounces of beer, 5 ounces of wine, 1½ ounces of 80-proof distilled spirits) * Potential candidates who are taking cardiovascular-acting (i.e. statins, blood pressure medication an aspirin) medications will not be eligible. * Fasting plasma glucose \>126 mg/dL. * Potential candidates with a resting heart rate of \< 50 beats/minute will be excluded. * Use of hormone replacement therapy. * In hypertensive subjects, a seated systolic blood pressure greater than 160 mmHg or a seated diastolic blood pressure greater than 100 mmHg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | — |
| Diastolic Blood Pressure | Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | — |
| Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | Forearm blood flow was measured at 0-60 minutes before the 12 week drug or placebo intervention and 0-60 minutes after the 12 week drug or placebo intervention. | Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion. |
| Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | Forearm blood flow was measured 0-120 minutes before the 12 week drug or placebo intervention and 0-120 minutes after the 12 week drug or placebo intervention. | Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion. |
| FBF Response to Acetylcholine (ACh) | Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | FBF was measured via strain-gauge occlusion plethysmography at rest and in response to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. |
| FBF Response to Sodium Nitroprusside | Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | FBF was measured via strain-gauge occlusion plethysmography at rest and in response to sodium nitroprusside (1.0, 2.0 and 4.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. |
| FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | FBF was measured via strain-gauge occlusion plethysmography at rest and in response to BQ-123+BQ-788 +ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks | 14 |
| Metoprolol Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks | 14 |
| Placebo Placebo: gelatin capsule to be taken by mouth once per day for 12 weeks | 14 |
| Total | 42 |
Baseline characteristics
| Characteristic | Metoprolol | Placebo | Nebivolol | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 4.1 | 56 years STANDARD_DEVIATION 5.9 | 57 years STANDARD_DEVIATION 5.3 | 56 years STANDARD_DEVIATION 5.1 |
| Region of Enrollment United States | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Diastolic Blood Pressure
Time frame: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Nebivolol | Diastolic Blood Pressure | 89 mmHg | Standard Error 5.2 |
| After Nebivolol | Diastolic Blood Pressure | 77 mmHg | Standard Error 5.3 |
| Before Metoprolol | Diastolic Blood Pressure | 90 mmHg | Standard Error 7.6 |
| After Metoprolol | Diastolic Blood Pressure | 77 mmHg | Standard Error 4.8 |
| Before Placebo | Diastolic Blood Pressure | 86 mmHg | Standard Error 7.7 |
| After Placebo | Diastolic Blood Pressure | 83 mmHg | Standard Error 7.3 |
Primary
FBF Response to Acetylcholine (ACh)
FBF was measured via strain-gauge occlusion plethysmography at rest and in response to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.
Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Before Nebivolol | FBF Response to Acetylcholine (ACh) | Baseline | 5.2 mL/100 mL tissue/min | Standard Error 0.3 |
| Before Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 13.3 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 12.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 12.1 mL/100 mL tissue/min | Standard Error 0.8 |
| After Nebivolol | FBF Response to Acetylcholine (ACh) | Baseline | 4.9 mL/100 mL tissue/min | Standard Error 0.4 |
| After Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 15.0 mL/100 mL tissue/min | Standard Error 0.8 |
| After Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 13.9 mL/100 mL tissue/min | Standard Error 0.9 |
| After Nebivolol | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 16.4 mL/100 mL tissue/min | Standard Error 0.6 |
| Before Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 13.1 mL/100 mL tissue/min | Standard Error 1.1 |
| Before Metoprolol | FBF Response to Acetylcholine (ACh) | Baseline | 5.3 mL/100 mL tissue/min | Standard Error 0.5 |
| Before Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 13.8 mL/100 mL tissue/min | Standard Error 1.1 |
| Before Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 12.4 mL/100 mL tissue/min | Standard Error 1 |
| After Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 12.0 mL/100 mL tissue/min | Standard Error 1 |
| After Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 14.1 mL/100 mL tissue/min | Standard Error 1.1 |
| After Metoprolol | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 13.2 mL/100 mL tissue/min | Standard Error 1.1 |
| After Metoprolol | FBF Response to Acetylcholine (ACh) | Baseline | 5.6 mL/100 mL tissue/min | Standard Error 0.5 |
| Before Placebo | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 12.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Placebo | FBF Response to Acetylcholine (ACh) | Baseline | 4.8 mL/100 mL tissue/min | Standard Error 0.2 |
| Before Placebo | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 12.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Before Placebo | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 11.4 mL/100 mL tissue/min | Standard Error 0.6 |
| After Placebo | FBF Response to Acetylcholine (ACh) | ACh 8.0 | 13.7 mL/100 mL tissue/min | Standard Error 0.6 |
| After Placebo | FBF Response to Acetylcholine (ACh) | ACh 16.0 | 13.9 mL/100 mL tissue/min | Standard Error 0.7 |
| After Placebo | FBF Response to Acetylcholine (ACh) | Baseline | 5.1 mL/100 mL tissue/min | Standard Error 0.3 |
| After Placebo | FBF Response to Acetylcholine (ACh) | ACh 4.0 | 13.2 mL/100 mL tissue/min | Standard Error 0.7 |
Primary
FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)
FBF was measured via strain-gauge occlusion plethysmography at rest and in response to BQ-123+BQ-788 +ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.
Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 11.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 14.6 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 12.9 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 15.3 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 5.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 15.9 mL/100 mL tissue/min | Standard Error 0.6 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 12.3 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 6.4 mL/100 mL tissue/min | Standard Error 0.5 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 13.8 mL/100 mL tissue/min | Standard Error 0.9 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 15.0 mL/100 mL tissue/min | Standard Error 0.7 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 4.7 mL/100 mL tissue/min | Standard Error 0.3 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 16.1 mL/100 mL tissue/min | Standard Error 0.5 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 13.7 mL/100 mL tissue/min | Standard Error 0.9 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 15.0 mL/100 mL tissue/min | Standard Error 0.7 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 14.5 mL/100 mL tissue/min | Standard Error 0.8 |
| After Nebivolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 5.8 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 17.1 mL/100 mL tissue/min | Standard Error 1.2 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 13.1 mL/100 mL tissue/min | Standard Error 1.1 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 16.1 mL/100 mL tissue/min | Standard Error 1.3 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 13.7 mL/100 mL tissue/min | Standard Error 1.2 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 6.7 mL/100 mL tissue/min | Standard Error 0.4 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 14.5 mL/100 mL tissue/min | Standard Error 1.2 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 5.5 mL/100 mL tissue/min | Standard Error 0.4 |
| Before Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 17.9 mL/100 mL tissue/min | Standard Error 1.3 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 13.7 mL/100 mL tissue/min | Standard Error 1.2 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 6.0 mL/100 mL tissue/min | Standard Error 0.5 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 16.5 mL/100 mL tissue/min | Standard Error 1.3 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 17.6 mL/100 mL tissue/min | Standard Error 1.2 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 12.4 mL/100 mL tissue/min | Standard Error 1.1 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 14.7 mL/100 mL tissue/min | Standard Error 1.2 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 7.4 mL/100 mL tissue/min | Standard Error 0.7 |
| After Metoprolol | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 18.2 mL/100 mL tissue/min | Standard Error 1.2 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 11.7 mL/100 mL tissue/min | Standard Error 0.6 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 13.0 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 15.1 mL/100 mL tissue/min | Standard Error 0.9 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 4.9 mL/100 mL tissue/min | Standard Error 0.2 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 13.5 mL/100 mL tissue/min | Standard Error 1 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 16.2 mL/100 mL tissue/min | Standard Error 0.9 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 12.3 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 6.1 mL/100 mL tissue/min | Standard Error 0.4 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0 | 13.3 mL/100 mL tissue/min | Standard Error 0.7 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0 | 13.9 mL/100 mL tissue/min | Standard Error 0.8 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline | 5.1 mL/100 mL tissue/min | Standard Error 0.3 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 16.0+BQ-123/788 | 17.3 mL/100 mL tissue/min | Standard Error 1 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0+BQ-123/788 | 16.5 mL/100 mL tissue/min | Standard Error 0.9 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 4.0+BQ-123/788 | 15.3 mL/100 mL tissue/min | Standard Error 0.9 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | ACh 8.0 | 13.7 mL/100 mL tissue/min | Standard Error 0.7 |
| After Placebo | FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788) | Baseline+BQ123/788 | 5.6 mL/100 mL tissue/min | Standard Error 0.4 |
Primary
FBF Response to Sodium Nitroprusside
FBF was measured via strain-gauge occlusion plethysmography at rest and in response to sodium nitroprusside (1.0, 2.0 and 4.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.
Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Before Nebivolol | FBF Response to Sodium Nitroprusside | Baseline | 5.2 mL/100 mL tissue/min | Standard Error 0.4 |
| Before Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 13.5 mL/100 mL tissue/min | Standard Error 1.2 |
| Before Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 15.3 mL/100 mL tissue/min | Standard Error 1.3 |
| Before Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 15.9 mL/100 mL tissue/min | Standard Error 1.2 |
| After Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 15.2 mL/100 mL tissue/min | Standard Error 1 |
| After Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 13.7 mL/100 mL tissue/min | Standard Error 1 |
| After Nebivolol | FBF Response to Sodium Nitroprusside | Baseline | 4.7 mL/100 mL tissue/min | Standard Error 0.3 |
| After Nebivolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 16.4 mL/100 mL tissue/min | Standard Error 1.1 |
| Before Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 15.8 mL/100 mL tissue/min | Standard Error 1.3 |
| Before Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 14.9 mL/100 mL tissue/min | Standard Error 1.3 |
| Before Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 14.1 mL/100 mL tissue/min | Standard Error 1.3 |
| Before Metoprolol | FBF Response to Sodium Nitroprusside | Baseline | 4.9 mL/100 mL tissue/min | Standard Error 0.3 |
| After Metoprolol | FBF Response to Sodium Nitroprusside | Baseline | 5.7 mL/100 mL tissue/min | Standard Error 0.5 |
| After Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 16.0 mL/100 mL tissue/min | Standard Error 1 |
| After Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 14.3 mL/100 mL tissue/min | Standard Error 1.2 |
| After Metoprolol | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 15.1 mL/100 mL tissue/min | Standard Error 1.1 |
| Before Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 14.4 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 15.8 mL/100 mL tissue/min | Standard Error 0.8 |
| Before Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 12.8 mL/100 mL tissue/min | Standard Error 0.7 |
| Before Placebo | FBF Response to Sodium Nitroprusside | Baseline | 5.2 mL/100 mL tissue/min | Standard Error 0.3 |
| After Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 1.0 | 13.7 mL/100 mL tissue/min | Standard Error 0.8 |
| After Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 2.0 | 15.3 mL/100 mL tissue/min | Standard Error 0.8 |
| After Placebo | FBF Response to Sodium Nitroprusside | Sodium Nitroprusside 4.0 | 16.1 mL/100 mL tissue/min | Standard Error 0.9 |
| After Placebo | FBF Response to Sodium Nitroprusside | Baseline | 5.2 mL/100 mL tissue/min | Standard Error 0.3 |
Primary
Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)
Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion.
Time frame: Forearm blood flow was measured 0-120 minutes before the 12 week drug or placebo intervention and 0-120 minutes after the 12 week drug or placebo intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 47.4 Percent change from baseline | Standard Error 7.8 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 44.0 Percent change from baseline | Standard Error 6.9 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 25.8 Percent change from baseline | Standard Error 4.6 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 41.3 Percent change from baseline | Standard Error 7 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 17.4 Percent change from baseline | Standard Error 3.3 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 39.5 Percent change from baseline | Standard Error 7.1 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 57.6 Percent change from baseline | Standard Error 9 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 47.6 Percent change from baseline | Standard Error 8.5 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | 10.2 Percent change from baseline | Standard Error 2.6 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 25.6 Percent change from baseline | Standard Error 6.3 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 27.0 Percent change from baseline | Standard Error 6.4 |
| Before Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | 22.3 Percent change from baseline | Standard Error 5.1 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 6.1 Percent change from baseline | Standard Error 3.6 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 21.8 Percent change from baseline | Standard Error 9.2 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | -1.1 Percent change from baseline | Standard Error 3.3 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 3.8 Percent change from baseline | Standard Error 3.2 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 1.1 Percent change from baseline | Standard Error 4.5 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 16.1 Percent change from baseline | Standard Error 8.2 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 9.2 Percent change from baseline | Standard Error 3.7 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 6.0 Percent change from baseline | Standard Error 3.3 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | -1.0 Percent change from baseline | Standard Error 1.7 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 22.3 Percent change from baseline | Standard Error 8.5 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 18.9 Percent change from baseline | Standard Error 7 |
| After Nebivolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 20.4 Percent change from baseline | Standard Error 7.6 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 49.8 Percent change from baseline | Standard Error 9.5 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 47.5 Percent change from baseline | Standard Error 7.4 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 44.7 Percent change from baseline | Standard Error 7.3 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 28.4 Percent change from baseline | Standard Error 4.9 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | 10.0 Percent change from baseline | Standard Error 3.7 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 31.4 Percent change from baseline | Standard Error 5.9 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | 23.0 Percent change from baseline | Standard Error 4.6 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 33.2 Percent change from baseline | Standard Error 6.9 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 18.0 Percent change from baseline | Standard Error 4.7 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 57.8 Percent change from baseline | Standard Error 10.4 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 64.6 Percent change from baseline | Standard Error 9.8 |
| Before Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 34.4 Percent change from baseline | Standard Error 5.7 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 27.7 Percent change from baseline | Standard Error 4.8 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | 11.1 Percent change from baseline | Standard Error 2.8 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 28.9 Percent change from baseline | Standard Error 3.8 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 30.6 Percent change from baseline | Standard Error 5.5 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 32.2 Percent change from baseline | Standard Error 7.3 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 47.4 Percent change from baseline | Standard Error 6.9 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 48.1 Percent change from baseline | Standard Error 7.6 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 55.4 Percent change from baseline | Standard Error 7.1 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 18.7 Percent change from baseline | Standard Error 3.2 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | 21.1 Percent change from baseline | Standard Error 4.8 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 37.8 Percent change from baseline | Standard Error 5.7 |
| After Metoprolol | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 42.0 Percent change from baseline | Standard Error 7.6 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 20.4 Percent change from baseline | Standard Error 3.1 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 33.8 Percent change from baseline | Standard Error 5.3 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 42.6 Percent change from baseline | Standard Error 9.5 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 29.0 Percent change from baseline | Standard Error 5.6 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 23.9 Percent change from baseline | Standard Error 4.3 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 57.9 Percent change from baseline | Standard Error 9.5 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 57.1 Percent change from baseline | Standard Error 9.5 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 37.5 Percent change from baseline | Standard Error 8.3 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | 13.1 Percent change from baseline | Standard Error 4.6 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 57.8 Percent change from baseline | Standard Error 7.8 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 46.4 Percent change from baseline | Standard Error 8.9 |
| Before Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | 26.8 Percent change from baseline | Standard Error 5.1 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 60 min | 30.4 Percent change from baseline | Standard Error 3.7 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 40 min | 25.7 Percent change from baseline | Standard Error 3.9 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 10 min | 15.7 Percent change from baseline | Standard Error 3 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 110 min | 52.8 Percent change from baseline | Standard Error 9.3 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 90 min | 47.1 Percent change from baseline | Standard Error 7.4 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 80 min | 45.0 Percent change from baseline | Standard Error 7.9 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 70 min | 38.0 Percent change from baseline | Standard Error 7.5 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 20 min | 14.7 Percent change from baseline | Standard Error 3.9 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 50 min | 26.5 Percent change from baseline | Standard Error 4.5 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 120 min | 49.5 Percent change from baseline | Standard Error 10.3 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123+BQ-788 100 min | 53.4 Percent change from baseline | Standard Error 8.5 |
| After Placebo | Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min) | BQ-123 30 min | 23.3 Percent change from baseline | Standard Error 4.5 |
Primary
Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)
Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion.
Time frame: Forearm blood flow was measured at 0-60 minutes before the 12 week drug or placebo intervention and 0-60 minutes after the 12 week drug or placebo intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 25.6 percent change from baseline | Standard Error 6.3 |
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | 22.3 percent change from baseline | Standard Error 5.1 |
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 27.0 percent change from baseline | Standard Error 6.4 |
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 17.4 percent change from baseline | Standard Error 3.3 |
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 25.8 percent change from baseline | Standard Error 4.6 |
| Before Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | 10.2 percent change from baseline | Standard Error 2.6 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 6.0 percent change from baseline | Standard Error 3.3 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 6.1 percent change from baseline | Standard Error 3.6 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 1.1 percent change from baseline | Standard Error 4.5 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | -1.0 percent change from baseline | Standard Error 1.7 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | -1.1 percent change from baseline | Standard Error 3.3 |
| After Nebivolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 3.8 percent change from baseline | Standard Error 3.2 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 28.4 percent change from baseline | Standard Error 4.9 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | 23.0 percent change from baseline | Standard Error 4.6 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 18.0 percent change from baseline | Standard Error 4.7 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 31.4 percent change from baseline | Standard Error 5.9 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 34.4 percent change from baseline | Standard Error 5.7 |
| Before Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | 10.0 percent change from baseline | Standard Error 3.7 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 30.6 percent change from baseline | Standard Error 5.5 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 18.7 percent change from baseline | Standard Error 3.2 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 28.9 percent change from baseline | Standard Error 3.8 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 27.7 percent change from baseline | Standard Error 4.8 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | 21.1 percent change from baseline | Standard Error 4.8 |
| After Metoprolol | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | 11.1 percent change from baseline | Standard Error 2.8 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | 26.8 percent change from baseline | Standard Error 5.1 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | 13.1 percent change from baseline | Standard Error 4.6 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 20.4 percent change from baseline | Standard Error 3.1 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 23.9 percent change from baseline | Standard Error 4.3 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 29.0 percent change from baseline | Standard Error 5.6 |
| Before Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 33.8 percent change from baseline | Standard Error 5.3 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 60 min | 30.4 percent change from baseline | Standard Error 3.7 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 50 min | 26.5 percent change from baseline | Standard Error 4.5 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 10 min | 15.7 percent change from baseline | Standard Error 3 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 30 min | 23.3 percent change from baseline | Standard Error 4.5 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 40 min | 25.7 percent change from baseline | Standard Error 3.9 |
| After Placebo | Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min) | BQ-123 20 min | 14.7 percent change from baseline | Standard Error 3.9 |
Primary
Systolic Blood Pressure
Time frame: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Nebivolol | Systolic Blood Pressure | 144 mmHg | Standard Error 6.6 |
| After Nebivolol | Systolic Blood Pressure | 126 mmHg | Standard Error 7.8 |
| Before Metoprolol | Systolic Blood Pressure | 140 mmHg | Standard Error 6.1 |
| After Metoprolol | Systolic Blood Pressure | 125 mmHg | Standard Error 9.3 |
| Before Placebo | Systolic Blood Pressure | 139 mmHg | Standard Error 4.9 |
| After Placebo | Systolic Blood Pressure | 134 mmHg | Standard Error 8.3 |