Prehypertension, Hypertension
Conditions
Brief summary
The investigators hypothesize that nebivolol will improve endothelial t-PA release in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo. The investigators further hypothesize that the improvement in the capacity of the vascular endothelium to release t-PA with nebivolol is mediated, in part, by the compound's antioxidant properties.
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
OTHERBradykinin
Bradykinin is infused into the brachial artery at doses of 12.5, 25.0 and 50.0 ng/100 mL of forearm tissue /min. BDK stimulates the endothelial cells to release tissue type plasminogen activator (t-PA). Blood flow in mL/100 mL tissue/min is also measured to BDK.
OTHERSaline
Baseline or resting forearm blood flow is measured in response to saline for 5 minutes before each drug infusion. t-PA release in response to the saline is also measured.
OTHERVitamin C
The acute effects of into-arterial vitamin C on the ability of the endothelium to release t-PA was determined before and after the nebivolol and metoprolol intervention. After allowing sufficient time (\ 20 minutes) for FBF and plasma t-PA concentrations to return to baseline following the initial infusion of BDK, vitamin C (24 mg/min) was infused at a constant rate while the BDK dose-response curves were repeated. t-PA and FBF were measured.
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 \>125 mmHg and \<160 mmHg and/or diastolic \>80 mmHg and \<100 mmHg. * All of the women in the study will be postmenopausal and not receiving hormone replacement therapy (HRT) currently or in the preceding 3-year period. * 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 and 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 \>160 mmHg or a seated diastolic blood pressure \>100 mmHg will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate | Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | Resting heart rate in the seated position |
| 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. | — |
| Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention. | Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. |
| Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention. | Net endothelial release of t-PA antigen in response to bradykinin (BDK) and bradykinin+vitamin C (BDK+C) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. |
| Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention. | Net endothelial release of t-PA antigen in response to BDK and BDK+C was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. |
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 | 16 |
| Metoprolol Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks | 16 |
| Placebo Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks | 12 |
| Total | 44 |
Baseline characteristics
| Characteristic | Nebivolol | Total | Placebo | Metoprolol |
|---|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 5 | 58 years STANDARD_DEVIATION 6 | 57 years STANDARD_DEVIATION 6 | 58 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 40 Participants | 11 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 39 Participants | 11 Participants | 14 Participants |
| Region of Enrollment United States | 16 participants | 44 participants | 12 participants | 16 participants |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 28 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 12 |
| other Total, other adverse events | 0 / 16 | 0 / 16 | 0 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 12 |
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 | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Diastolic Blood Pressure | Before Intervention | 85 mmHg | Standard Error 2 |
| Nebivolol | Diastolic Blood Pressure | After Intervention | 78 mmHg | Standard Error 2 |
| Metoprolol | Diastolic Blood Pressure | Before Intervention | 87 mmHg | Standard Error 2 |
| Metoprolol | Diastolic Blood Pressure | After Intervention | 79 mmHg | Standard Error 2 |
| Placebo | Diastolic Blood Pressure | Before Intervention | 85 mmHg | Standard Error 3 |
| Placebo | Diastolic Blood Pressure | After Intervention | 81 mmHg | Standard Error 2 |
Primary
Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
Net endothelial release of t-PA antigen in response to BDK and BDK+C was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Time frame: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to Saline | -2.7 ng/100 mL tissue/min | Standard Error 0.9 |
| Nebivolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 25.0 | 24.5 ng/100 mL tissue/min | Standard Error 3.8 |
| Nebivolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 50.0 | 45.0 ng/100 mL tissue/min | Standard Error 5.5 |
| Nebivolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 12.5 | 10.1 ng/100 mL tissue/min | Standard Error 3.9 |
| Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 50.0 | 82.4 ng/100 mL tissue/min | Standard Error 10.2 |
| Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 25.0 | 47.1 ng/100 mL tissue/min | Standard Error 7.3 |
| Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to Saline | -2.5 ng/100 mL tissue/min | Standard Error 0.8 |
| Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 12.5 | 31.1 ng/100 mL tissue/min | Standard Error 5 |
| Placebo | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 50.0 | 49.9 ng/100 mL tissue/min | Standard Error 5.7 |
| Placebo | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 25.0 | 31.3 ng/100 mL tissue/min | Standard Error 3.3 |
| Placebo | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 12.5 | 16.4 ng/100 mL tissue/min | Standard Error 5 |
| Placebo | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to Saline | -1.3 ng/100 mL tissue/min | Standard Error 1.4 |
| After Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 50.0 | 73.8 ng/100 mL tissue/min | Standard Error 7.4 |
| After Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to Saline | -2.7 ng/100 mL tissue/min | Standard Error 1.1 |
| After Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 12.5 | 30.0 ng/100 mL tissue/min | Standard Error 4.4 |
| After Metoprolol | Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy. | Amount of t-PA release to BDK 25.0 | 46.4 ng/100 mL tissue/min | Standard Error 6.3 |
Primary
Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
Net endothelial release of t-PA antigen in response to bradykinin (BDK) and bradykinin+vitamin C (BDK+C) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Time frame: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to saline | -2.4 ng/100 mL tissue/min | Standard Error 1.1 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 12.5 | 14.3 ng/100 mL tissue/min | Standard Error 3.2 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 25.0 | 27.6 ng/100 mL tissue/min | Standard Error 5 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 50.0 | 47.2 ng/100 mL tissue/min | Standard Error 5 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 12.5 | 31.3 ng/100 mL tissue/min | Standard Error 5.5 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 25.0 | 52.7 ng/100 mL tissue/min | Standard Error 6.6 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 50.0 | 80.5 ng/100 mL tissue/min | Standard Error 6.2 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to saline | -1.4 ng/100 mL tissue/min | Standard Error 0.8 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 25.0 | 49.1 ng/100 mL tissue/min | Standard Error 9.1 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 12.5 | 28.2 ng/100 mL tissue/min | Standard Error 6.2 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 50.0 | 67.5 ng/100 mL tissue/min | Standard Error 7.1 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to saline | -1.5 ng/100 mL tissue/min | Standard Error 1.3 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 50.0 | 79.9 ng/100 mL tissue/min | Standard Error 7.6 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 12.5 | 38.1 ng/100 mL tissue/min | Standard Error 7.3 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to saline | -3.8 ng/100 mL tissue/min | Standard Error 2.6 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy. | Amount of t-PA release to BDK 25.0 | 54.2 ng/100 mL tissue/min | Standard Error 7.9 |
Primary
Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Time frame: t-PA release 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 |
|---|---|---|---|---|
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -1.2 ng/100 mL tissue/min | Standard Error 0.8 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 15.7 ng/100 mL tissue/min | Standard Error 2.9 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 29.1 ng/100 mL tissue/min | Standard Error 3.9 |
| Nebivolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 47.2 ng/100 mL tissue/min | Standard Error 4.3 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 46.4 ng/100 mL tissue/min | Standard Error 6.5 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 25.2 ng/100 mL tissue/min | Standard Error 4.1 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -1.8 ng/100 mL tissue/min | Standard Error 0.9 |
| Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 72.8 ng/100 mL tissue/min | Standard Error 5.7 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 48.2 ng/100 mL tissue/min | Standard Error 5.9 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 27.5 ng/100 mL tissue/min | Standard Error 3.3 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 14.4 ng/100 mL tissue/min | Standard Error 3.3 |
| Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -1.2 ng/100 mL tissue/min | Standard Error 1.2 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -1.9 ng/100 mL tissue/min | Standard Error 1.1 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 52.7 ng/100 mL tissue/min | Standard Error 4.6 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 16.6 ng/100 mL tissue/min | Standard Error 3.3 |
| After Metoprolol | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 31.2 ng/100 mL tissue/min | Standard Error 2.4 |
| Before Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 28.3 ng/100 mL tissue/min | Standard Error 3.8 |
| Before Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 51.1 ng/100 mL tissue/min | Standard Error 5 |
| Before Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 18.1 ng/100 mL tissue/min | Standard Error 3.1 |
| Before Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -0.2 ng/100 mL tissue/min | Standard Error 1.2 |
| After Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 12.5 | 17.6 ng/100 mL tissue/min | Standard Error 2.8 |
| After Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 25.0 | 32.7 ng/100 mL tissue/min | Standard Error 5.6 |
| After Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to BDK 50.0 | 52.9 ng/100 mL tissue/min | Standard Error 4.3 |
| After Placebo | Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention | Amount of t-PA release to Saline | -0.9 ng/100 mL tissue/min | Standard Error 1.5 |
Primary
Heart Rate
Resting heart rate in the seated position
Time frame: Heart rate 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 |
|---|---|---|---|---|
| Nebivolol | Heart Rate | Before Intervention | 64 bpm | Standard Error 1 |
| Nebivolol | Heart Rate | After Intervention | 58 bpm | Standard Error 2 |
| Metoprolol | Heart Rate | Before Intervention | 71 bpm | Standard Error 1 |
| Metoprolol | Heart Rate | After Intervention | 64 bpm | Standard Error 3 |
| Placebo | Heart Rate | Before Intervention | 69 bpm | Standard Error 2 |
| Placebo | Heart Rate | After Intervention | 72 bpm | Standard Error 2 |
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 | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Systolic Blood Pressure | After Intervention | 125 mmHg | Standard Error 2 |
| Nebivolol | Systolic Blood Pressure | Before Intervention | 140 mmHg | Standard Error 2 |
| Metoprolol | Systolic Blood Pressure | After Intervention | 125 mmHg | Standard Error 3 |
| Metoprolol | Systolic Blood Pressure | Before Intervention | 138 mmHg | Standard Error 2 |
| Placebo | Systolic Blood Pressure | Before Intervention | 138 mmHg | Standard Error 2 |
| Placebo | Systolic Blood Pressure | After Intervention | 135 mmHg | Standard Error 3 |