Mechanisms of Exercise Pressor Reflex Overactivity in Hypertension

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DESCRIPTION (provided by applicant): In hypertensive individuals, exercise elicits excessive increases in arterial blood pressure, heart rate and vascular resistance. These potentially dangerous elevations in circulatory hemodynamics increase the risk for adverse cardiac events or stroke during exercise. We have previously established that overactivity of the exercise pressor reflex, a circulatory reflex originating within skeletal muscle, contributes importantly to the generation of these heightened cardiovascular responses. Further, evidence from our laboratory suggests that both the muscle mechanoreflex and metaboreflex, the two functional components of the exercise pressor reflex, drive this overactivity. However, the mechanisms underlying exercise pressor reflex dysfunction in hypertension are not clear. Sensory information generated by activation of the exercise pressor reflex is processed within the nucleus tractus solitarius (NTS) of the medulla oblongata. The activity of neurons within the medulla that receive and process this information can be modulated by the endogenous production of nitric oxide (NO). NO production is mediated by nitric oxide synthase (NOS). Likewise, NO activity within the NTS can be modified by the generation of reactive oxygen species (ROS). Therefore, alterations in either NOS expression/activity or ROS production potentially contribute to changes in NO activity within the NTS. As such, the NO pathway within the NTS represents a viable target for disease induced alterations in exercise pressor reflex function. Based on this knowledge, we hypothesize that the enhanced cardiovascular response to exercise mediated by the exercise pressor reflex in hypertension is induced by alterations in NO activity, changes in NOS expression and/or function as well as alterations in the generation of ROS within the NTS. To test these hypotheses, we will perform physiologic and neuro-biochemical studies in normotensive and hypertensive rats to address the following specific aims: 1) determine the role of NO within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension; 2) determine the role of NOS within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension; and 3) determine the role of ROS within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension.