Cheese Consumption and Human Microvascular Function
Condition: Microvascular Dysfunction
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Acetylcholine (ACh) Dose Response; Local Heating (LH); Flow Mediated Dilation with nitroglycerin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin; Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin; BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.
Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.
Other intervention name(s): ACh Dose Response; LH; FMD
Intervention MeSH terms: Nitroglycerin; Acetylcholine
Allocation: Randomized
Intervention model: Crossover Assignment
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.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Sodium; Hypertension; Blood Pressure; Cardiovascular Disease; Nitric Oxide; Skin; Dairy; Cheese; Oxidative Stress; Diet; Flow Mediated Vasodilation; Nitroglycerin; Superoxide; Microcirculation