Gary Pierce

The glycocalyx serves as the interface between flowing blood and endothelial cells, the single cell layer that lines blood vessels, and is crucial for normal blood vessel function. Specifically, the glycocalyx protects endothelial cells from oxidative stress and inflammation and enables blood vessel dilation, which is largely dependent on the bioavailability of the vasodilatory molecule nitric oxide. Importantly, glycocalyx thickness decreases with age and is predictive of major adverse cardiovascular events in older adults free of cardiovascular disease. Therefore, interventions aimed at restoring glycocalyx thickness in older adults are desperately needed. Endocalyx Pro is a commercially available glycocalyx precursor supplement, manufactured by Microvascular Health Solutions, designed to 1) repair a damaged glycocalyx, 2) protect against damage to the glycocalyx, and 3) synthesize new glycocalyx components, and has been used to increase glycocalyx thickness in humans. However, no study has tested if glycocalyx thickness restores glycocalyx thickness in older adults and improves blood vessel function. Thus, the purpose of this investigation is to determine if 12-weeks of Endocalyx Pro supplementation alters glycocalyx thickness and blood vessel function in older adults. The investigators will use a camera placed under the tongue to determine glycocalyx thickness. The investigators will measure blood vessel function by measuring brachial artery dilation with ultrasound and arterial stiffness using pressure probes placed on the carotid and femoral artery.

Stiffening of your blood vessels, particularly the large vessels from your heart (called the aorta and carotids) you age contributes to the development of cardiovascular disease (CVD) such as heart attack and stroke. Nerve activity from your brain to your body also increases with advancing age but it is unknown if this nerve activity contributes directly to the stiffening on your blood vessels in older adults in addition to high blood pressure. Therefore, successful completion of the proposed aims will have a significant clinical impact by identifying if nerve activity from your brain could be a novel target for therapies that would lower stiffness of the aorta and carotid arteries in older adults.

This study investigates the effect of dietary inorganic nitrate supplementation on 1) large elastic artery stiffness and hemodynamics and 2) cerebrovascular function in middle-aged and older adults. Participants will be randomized to consume either nitrate-containing or nitrate-depleted beetroot juice.

The purpose of the study is to test the effects of blocking sympathetic nerve activity with a drug called clonidine on blood vessel function and muscle nerve activity in adults who are obese and have high blood pressure.

The cohort of subjects will consist of 69 healthy young men and women age 18-79 years who are obese, defined as a body mass index \> or = to 30 kg/m2, who have untreated systolic hypertension (systolic blood pressure \> or = to 130 - \<180 mmHg- average of at least 3 measurements 2 min apart after 10 min seated resting position). These 69 subjects will then be randomized to 3 treatment arms: clonidine (0.1 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks in years 1 and 2. All tablets will be encapsulated by to look identical. Subjects will randomly (1:1:1) receive one of the following combinations in a double-blind, placebo-controlled design:

1. Oral clonidine (0.1 mg twice/day)
2. Oral hydrochlorothiazide (12.5 mg twice/day)
3. Oral placebo

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