The applicant's career goal is to conduct independent cardiovascular research in an academic institution. The long- term objective of his research is to explore mechanisms of integrative control of cardiovascular function. This career award will increase substantially his productivity and solidify his establishment as a contributing scientist in this research area. The Wake Forest University School of Medicine provides a supportive environment for the continued development of his research career. The goal of the proposal is to establish an independent research program that will provide insights into the mechanisms governing integrative control of regional blood flows and systemic circulation. Ischemic stimulation of visceral afferents has profound impact on systemic circulation. Sympathetic efferent discharges to the heart and various vascular beds play an important role in cardiovascular reflexes. However, the mechanisms concerning sympathetic discharges during ischemia are not fully known. In this application, he will investigate a complex interaction among vagal afferents, vasopressin, sympathetic efferent nerves and the splanchnic circulation in integrative cardiovascular control during myocardial and mesenteric ischemia. The central hypothesis to be tested in the proposal is that ischemic stimulation of cardiac and abdominal afferents reflexly augments the splanchnic sympathetic outflows through a mechanism of spatiotemporal summation of efferent nerve discharges. This mechanism, in turn, causes a greater reduction of splanchnic blood flow to increase the blood pressure followed by secondary increases in heart rate and myocardial contractility. Increased splanchnic sympathetic outflow is also regulated by circulating Vasopressin due to activation of abdominal vagal afferents during mesenteric ischemia. These studies will yield new information as to how the cardiovascular and sympathetic discharges are influenced by vagal afferents and vasopressin during ischemia. Such information will improve our understanding of the mechanisms of integrative control of cardiovascular function by sensory and autonomic nervous systems in pathophysiological states.
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