Hypertension affects nearly 1 in 3 of all adults in the U.S. and is well recognized as a major risk factor for a broad range of cardiovascular diseases such as stroke, renal disease, and congestive heart failure. When hypertensive patients engage in strenuous exercise, sympathetic nerve activity can rise to dangerously high levels causing markedly exaggerated increases in arterial pressure and heart rate which increase the probability of sudden, adverse cardiovascular events such as myocardial infarction and stroke. The mechanisms mediating these abnormal cardiovascular responses to exercise in hypertension are unknown. Many studies have shown that activation of the metabolically sensitive afferents within the active skeletal muscle (termed the muscle metaboreflex) can elicit profound increases in sympathetic nerve activity. Impaired cardiac function in hypertension due to elevated afterload, cardiac hypertrophy, tonic coronary vasoconstriction and impaired ability to increase ventricular contractility may lead to lower skeletal muscle blood flow during exercise thereby causing excessive activation of the muscle metaboreflex. Furthermore, the mechanisms of the muscle metaboreflex are intimately dependent on the arterial baroreflex. Although, there is evidence that hypertension impairs baroreflex function at rest, whether exercise further alters baroreflex function in hypertension is unknown. This proposal is focused on determining the role of the muscle metaboreflex in mediating the altered cardiovascular response to dynamic exercise and the involvement of the arterial baroreflex in mediating these responses. Our laboratory is uniquely poised to address this issue. Over the last two decades we have developed a highly innovative and technically complex conscious, chronically instrumented canine model using state of the art instrumentation which permits the continuous beat-by-beat monitoring of systemic hemodynamic parameters and multiple indices of ventricular function in order to assess the strength and mechanisms of cardiovascular reflexes at rest and during dynamic exercise in normal animals and after induction of disease states. We have expanded this model to the patho-physiological state of hypertension. We propose the first longitudinal study of the effects of hypertension on integrative mechanisms mediating neural control of cardiovascular function during exercise. Our approach is to study the same animal before and after the induction of hypertension thereby each animal serves as its own control. These results may aid in the prescription of exercise regimes for hypertensive patients as well as increasing our understanding of the impact of hypertension on neural control of the circulation during one of the greatest challenges to cardiovascular control - whole body strenuous dynamic exercise.
Hypertension affects nearly 1 in 3 of all adults in the U.S. and is well recognized as a major risk factor for a broad range of cardiovascular diseases such as stroke, atherosclerosis, renal disease, and congestive heart failure. In patients with well-established hypertension excessively large increases in sympathetic activity, arterial pressure and heart rate in response to exercise often occur which may preclude advisement of any strenuous physical activity due to the dangerous elevations in sympathetic activity and arterial pressure which increase the probability of sudden, adverse cardiovascular events such as myocardial infarction, arrhythmias, sudden cardiac death and stroke. The mechanisms mediating these extreme cardiovascular responses to exercise in hypertension are virtually unknown. This proposal is focused on determining the role of sensory nerves that respond to changes in metabolite concentration in the active muscles and those that sense changes in blood pressure in mediating these severe responses to exercise in hypertension.
| Kaur, Jasdeep; Senador, Danielle; Krishnan, Abhinav C et al. (2018) Muscle metaboreflex-induced vasoconstriction in the ischemic active muscle is exaggerated in heart failure. Am J Physiol Heart Circ Physiol 314:H11-H18 |
| Senador, Danielle; Kaur, Jasdeep; Alvarez, Alberto et al. (2017) Role of endothelial nitric oxide in control of peripheral vascular conductance during muscle metaboreflex activation. Am J Physiol Regul Integr Comp Physiol 313:R29-R34 |
| Spranger, Marty D; Kaur, Jasdeep; Sala-Mercado, Javier A et al. (2017) Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension. Am J Physiol Heart Circ Physiol 312:H68-H79 |
| Zucker, Irving H; Lindsey, Merry L; Delmar, Mario et al. (2017) Why publish in the American Journal of Physiology-Heart and Circulatory Physiology? Am J Physiol Heart Circ Physiol 313:H221-H223 |
| Ardell, J L; Andresen, M C; Armour, J A et al. (2016) Translational neurocardiology: preclinical models and cardioneural integrative aspects. J Physiol 594:3877-909 |
