Understanding the Exercise-Hypertension Paradox
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      Nearly 37% of all Veterans are clinically hypertensive, making hypertension the most common
      medical condition in the VA Health Care System. Importantly, of the 67 million Americans
      diagnosed with hypertension less than half are being effectively treated for their condition.
      Hypertension constitutes a major risk factor for cardiovascular disease and when left
      untreated leads to the development of heart failure, coronary heart disease, peripheral
      artery disease, stroke, and renal disease. Exercise and regular physical activity are
      considered the cornerstones of prevention and management of hypertension. However,
      individuals with hypertension exhibit exercise intolerance characterized by impaired skeletal
      muscle blood flow and heightened afferent fiber sensitivity leading to an exaggerated or
      greater than normal physiologic increase in blood pressure during exercise (i.e. exercise
      pressor reflex or EPR). This imbalance between the beneficial effects of exercise and
      exercise intolerance creates an interesting paradox, the causes and consequences of which are
      poorly understood. The etiology of hypertension is undoubtedly complex, however a common
      denominator in this condition, elevated oxidative stress, may contribute to impaired muscle
      blood flow and heightened skeletal muscle afferent feedback leading to the exaggerated EPR.
      Previous work from the investigators' laboratory and others suggests that elevated oxidative
      stress associated with aging impairs muscle blood flow. Additionally, free radicals, the
      initiators of oxidative stress, can directly stimulate skeletal muscle afferent fibers
      leading to the exaggerated EPR. Importantly, the role of oxidative stress in regulating
      muscle blood flow and afferent fiber function in human hypertension has not been determined.
      Preliminary studies support a significant role of oxidative stress in impairing muscle blood
      flow and contributing to the exaggerated EPR in hypertension. With this information as
      context two aims are proposed that will systematically identify the consequences of elevated
      oxidative stress in hypertension. Specific Aim 1 will determine the consequences of oxidative
      stress by examining how elevated free radicals contribute to heightened skeletal muscle
      afferent feedback and impaired muscle blood flow during exercise in hypertension leading to
      the exaggerated EPR. Additionally, vascular endothelial cells collected from an antecubital
      vein will provide novel insight regarding the endothelium as potential source of elevated
      oxidative stress in hypertension. Specific Aim 2 will determine the effectiveness of combined
      antioxidant therapy and exercise rehabilitation in the treatment of hypertension. The overall
      goal of this proposal is to provide novel information regarding the role of oxidative stress
      as a critical regulator of cardiovascular and hemodynamic responses to exercise in
      hypertension. By identifying potential causes and consequences of oxidative stress, important
      insight will be gained facilitating the development of novel approaches and therapeutic
      strategies for the treatment of hypertension. Importantly, the practical applications tested
      in these studies (i.e. antioxidant treatment and combined exercise rehabilitation) are
      designed to identify and document effective countermeasures to aid in the treatment and
      management of hypertension allowing for the safe performance of exercise in a large number of
      Veterans.
    

Intervention name(s): Oral Antioxidant; Exercise rehabilitation
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Consisting of vitamins C, E and alpha lipoic acid.; 8 weeks of exercise rehabilitation
Intervention MeSH terms: Antioxidants
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Exercise