Microvascular Dysfunction
Conditions
Keywords
Sodium, Hypertension, Blood Pressure, Cardiovascular Disease, Nitric Oxide, Skin, Dairy, Cheese, Oxidative Stress, Diet, Flow Mediated Vasodilation, Nitroglycerin, Superoxide, Microcirculation
Brief summary
Increased dairy intake is associated with improved measures of blood vessel health. Dairy cheese, however, is often high in sodium. Dietary sodium can impair blood vessel function. The researchers examine if and how natural cheese may protect against impairments in blood vessel function caused by sodium. For this study, participants complete four 8-day controlled feeding periods in which they eat cheese (6 oz/day) or no cheese during a low-sodium or high-sodium base-diet. The participants complete baseline experiments while on their normal personal diet and then repeat experiments at the end of each controlled feeding period. In some of our experiments, the researchers use a technique called microdialysis (MD). With MD, the researchers perfuse some research drugs into the skin on the forearm through tiny tubing that mimics capillaries. These MD drugs mimic or block substances the body naturally makes to control the small blood vessels in the skin. The drugs remain in nickel-sized areas around the tubing and do not go into the rest of the body. The researchers also use a standard technique called flow mediated dilation (FMD) that uses blood pressure cuffs and ultrasound to look at the health of larger blood vessels in the body. FMD includes placing a small tablet of nitroglycerin under the tongue during part of the test.
Detailed description
Subject screening will be performed by the Penn State Clinical Translational Research Center (CTRC) medical staff and will include a physical exam by a clinician, anthropometry, and a chemical and lipid profile, liver and renal function. Participants meet with a registered dietitian to determine their caloric energy requirements and identify food preferences. The interview includes surveying the subject's physical activity over the previous 7 days. Subjects will undergo baseline microdialysis experiments to examine the function of the blood vessels in the skin microcirculation. Subjects will also go through a baseline assessment of conduit vessel endothelial and vascular smooth muscle function with brachial artery flow-mediated vasodilation (FMD), and sublingual nitroglycerin. Following baseline experiments, subjects participate in 4 controlled feeding periods, each 8 days in duration. The controlled feeding periods are assigned in a randomized order. At the end of each 8-day controlled dietary period, subjects will repeat microdialysis experiments, brachial artery FMD, and responsiveness to sublingual nitroglycerin.
Interventions
Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese 8 days
Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days
Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese 8 days
Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days
Sponsors
Study design
Masking description
Investigator and Outcomes Assessor are masked according to treatment.
Intervention model description
All subjects participate in 4 diets in randomized order. The diets differ in the amount of sodium and dairy cheese content. Each diet is consumed for 8 days. Minimum washout of 1 week between diets. Baseline experiment is conducted prior to first dietary intervention, and the experiment is repeated after each dietary intervention.
Eligibility
Inclusion criteria
* Seated systolic pressure 120-140 mmHg * Seated diastolic pressure 70-90 mmHg. * Normoglycemic (HbA1C \<5.7%)
Exclusion criteria
* Taking pharmacotherapy that alters peripheral vascular control * Pregnancy * Breastfeeding * Females taking contraceptives (pills, patches, shots, etc.) or hormone replacement therapy * Taking illicit and/or recreational drugs * Use of nicotine containing-products (e.g. smoking, chewing tobacco, etc.) * Known allergy to latex or investigative substances
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular Reactivity to Acetylcholine | 1 hour | Skin blood flow is measured with laser Doppler flowmetry (flux units) and normalized to cutaneous vascular conductance by dividing by mean arterial pressure. Log molar increasing concentrations of acetylcholine are perfused and dose response curves are generated. Dose response curves were analyzed to determine the logEC50 (log Molar) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | 8 days | Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The peak blood pressure during a cardiac cycle when the heart contracts. |
| Diastolic Blood Pressure | 8 days | Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The lowest blood pressure during a cardiac cycle when the heart is between beats. |
| Flow Mediated Dilation | 8 days | Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery. |
Countries
United States
Participant flow
Recruitment details
July 2017 to October 2019, Centre County, PA
Pre-assignment details
Subjects were enrolled in 4 separate 8-d controlled feeding interventions in a randomized, crossover study design. All food and beverages were prepared by a registered dietitian in the Pennsylvania State Clinical Research Center Metabolic Kitchen. Investigators involved in data collection and analysis were blinded to the dietary treatment.
Participants by arm
| Arm | Count |
|---|---|
| Sodium and Dairy Interventions low sodium no cheese low sodium cheese high sodium no cheese high sodium cheese baseline | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Sodium and Dairy Interventions |
|---|---|
| Age, Customized age | 64 years STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
Microvascular Reactivity to Acetylcholine
Skin blood flow is measured with laser Doppler flowmetry (flux units) and normalized to cutaneous vascular conductance by dividing by mean arterial pressure. Log molar increasing concentrations of acetylcholine are perfused and dose response curves are generated. Dose response curves were analyzed to determine the logEC50 (log Molar)
Time frame: 1 hour
Population: Data were collected with Windaq (Dataq Instruments) at a frequency of 40 Hz. CVC was calculated as red blood cell flux,. ACh dose concentrations were log-transformed and CVC was expressed as a percentage of maximum. Pharmacological curve modeling was performed using a 4-parameter, nonlinear regression with a variable slope to detect between-diet differences in microvascular sensitivity logEC50 (log Molar) of the group mean curve\] to ACh.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Microvascular Reactivity to Acetylcholine | -4.90 log (M) | Standard Error 0.2 |
| Low Sodium, No Cheese | Microvascular Reactivity to Acetylcholine | -4.82 log (M) | Standard Error 0.2 |
| Low Sodium, Cheese | Microvascular Reactivity to Acetylcholine | -5.44 log (M) | Standard Error 0.2 |
| High Sodium, No Cheese | Microvascular Reactivity to Acetylcholine | -3.21 log (M) | Standard Error 0.55 |
| High Sodium, Cheese | Microvascular Reactivity to Acetylcholine | -3.21 log (M) | Standard Error 0.55 |
Diastolic Blood Pressure
Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The lowest blood pressure during a cardiac cycle when the heart is between beats.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Diastolic Blood Pressure | 81 mmHg | Standard Error 1 |
| Low Sodium, No Cheese | Diastolic Blood Pressure | 75 mmHg | Standard Error 1 |
| Low Sodium, Cheese | Diastolic Blood Pressure | 74 mmHg | Standard Error 1 |
| High Sodium, No Cheese | Diastolic Blood Pressure | 78 mmHg | Standard Error 1 |
| High Sodium, Cheese | Diastolic Blood Pressure | 76 mmHg | Standard Error 1 |
Flow Mediated Dilation
Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Flow Mediated Dilation | 3.78 percentage of flow mediated vasodilation | Standard Error 0.78 |
| Low Sodium, No Cheese | Flow Mediated Dilation | 5.07 percentage of flow mediated vasodilation | Standard Error 0.9 |
| Low Sodium, Cheese | Flow Mediated Dilation | 4.20 percentage of flow mediated vasodilation | Standard Error 0.76 |
| High Sodium, No Cheese | Flow Mediated Dilation | 3.45 percentage of flow mediated vasodilation | Standard Error 1.04 |
| High Sodium, Cheese | Flow Mediated Dilation | 5.90 percentage of flow mediated vasodilation | Standard Error 1.34 |
Systolic Blood Pressure
Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The peak blood pressure during a cardiac cycle when the heart contracts.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Systolic Blood Pressure | 125 mmHg | Standard Error 1 |
| Low Sodium, No Cheese | Systolic Blood Pressure | 122 mmHg | Standard Error 2 |
| Low Sodium, Cheese | Systolic Blood Pressure | 121 mmHg | Standard Error 3 |
| High Sodium, No Cheese | Systolic Blood Pressure | 127 mmHg | Standard Error 3 |
| High Sodium, Cheese | Systolic Blood Pressure | 124 mmHg | Standard Error 3 |