Understanding the Exercise-Hypertension Paradox

Recruiting in Palo Alto (17 mi)

Overseen byJoel Douglas Trinity, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: VA Office of Research and Development

No Placebo Group

Trial Summary

What is the purpose of this trial?

Hypertension affects 37% of the Veteran population, making it the most common medical condition treated by the VA Health Care System. Physical activity is the first line of defense in the treatment and management of hypertension. However, individuals with hypertension have impaired muscle blood flow and exhibit exaggerated increases in blood pressure during exercise (exercise pressor reflex or EPR) leading to exercise intolerance and increased risk of stroke and heart attack. The cause of these impairments is not known, but it is highly likely that free radical production and the subsequent increase in oxidative stress plays a significant role. Two aims are proposed; Aim 1 will identify the physiological consequences of elevated oxidative stress in hypertension, and Aim 2 will utilize an antioxidant treatment to ameliorate the effects of an exaggerated EPR allowing the safe performance of a clinical exercise rehabilitation program which will then, itself, attenuate the EPR and reduce hypertension.

Research Team

Joel Douglas Trinity, PhD

Principal Investigator

VA Salt Lake City Health Care System, Salt Lake City, UT

Eligibility Criteria

Inclusion Criteria

A total of 72 middle-aged (40 - 60 years of age) healthy and hypertensive men and women will participate in these protocols after providing written informed consent.

The investigators aim to include a 1 to 1 ratio of females and males in each group.

Individuals diagnosed or presenting with stage 1 and stage 2 hypertension (range 140/90 to 179/109 mmHg, according to the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP) may be eligible for this study.

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Treatment Details

Interventions

Exercise rehabilitation (Behavioural Intervention)
Oral Antioxidant (Antioxidant)

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Specific Aim #2Experimental Treatment2 Interventions

Specific Aim 2: Determine the remediable effect of combined antioxidant treatment and exercise rehabilitation in the treatment of hypertension. Hypothesis: Acute antioxidant treatment administered prior to exercise in hypertensive patients will ameliorate the exaggerated EPR resulting in a normal and safe blood pressure response to exercise-based rehabilitation. This two-pronged approach (antioxidants and exercise training) will result in a safely achieved reduction in skeletal muscle afferent feedback facilitating improved exercise tolerance, improved muscle blood flow and ultimately reduced cardiovascular risk in this population.

Group II: Specific Aim #1Experimental Treatment1 Intervention

Specific Aim 1: Determine the consequences of oxidative stress on skeletal muscle afferent feedback and muscle blood flow during exercise in hypertension. Hypothesis: Afferent feedback sensitivity, determined by passive leg movement (isolation of mechanoreceptor sensitivity) and post exercise circulatory occlusion (isolation of metaboreceptor sensitivity) will be greater in hypertension leading to the exaggerated EPR. Muscle blood flow, assessed by Doppler ultrasound during multiple exercise intensities, will be impaired in hypertension leading to exercise intolerance. Reductions in oxidative stress, achieved by an oral antioxidant treatment (Vitamins C, E and alpha lipoic acid), will reduce afferent fiber sensitivity and improve muscle blood flow in hypertension. Additionally, venous endothelial cells will express elevated markers of oxidative stress providing novel evidence that the vascular endothelium contributes to the greater oxidative stress in hypertension.