Rehabilitation for Hypertension: Exercise and Skeletal Muscle Afferent Feedback

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): 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 only 31 million are being effectively treated, leaving 36 million (54%) Americans with uncontrolled hypertension. 1. Hypertension is 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 disease2, 3. Exercise and regular physical activity are considered the cornerstones of prevention and management of hypertension 2-4. Unfortunately, individuals with hypertension exhibit marked exercise intolerance5 and are characterized by an exaggerated or greater than normal physiologic increase in blood pressure during exercise (i.e. exercise pressor reflex or EPR)6-8. This excessive EPR increases the risk of adverse cardiovascular events such as myocardial infarction, cardiac arrest, or stroke during or immediately after exercise 7, 8 and is an established risk factor for cardiovascular morbidity and mortality 9, 10. This paradox is poorly understood, but it is highly likely that free radical production and the subsequent increase in oxidative stress plays a significant role in this response11-13. We have recently identified that afferent fibers, located in the skeletal muscle, play an essential role in regulating the cardiovascular response to exercise by increasing heart rate and blood pressure14. A process that in other pathologies, such as heart failure, has been documented to be influenced by oxidative stress. In hypertension these afferent fibers may be oversensitive to the free radical stimulus resulting in excessive increases in heart rate and blood pressure, ultimately leading to impaired blood flow and exercise intolerance. Two aims are proposed, the first will confirm a role of free radicals and oxidative stress in the exaggerated EPR in hypertension and the second will utilize an antioxidant cocktail to ameliorate the effects of an exaggerated EPR in hypertensive patients allowing the safe performance of a clinical exercise rehabilitation program which will then itself attenuate the EPR and reduce the level of hypertension.