The importance of the sympathetic nervous system in cardiovascular control during stressful situations, is axiomatic. Recently, a potent system for modulation of sympathetic activity by endogenous opioid peptides has been described. In the conscious, intact animal, this system is apparently involved with limiting sympathetic activation during blood loss. Although this system may function in a variety of stressful situations, our investigation will focus on its role during hemorrhagic hypotension. The general hypothesis is that endogenous opioid peptides both centrally and peripherally modulate autonomic nervous system function and thus cardiovascular control during periods of elevated sympathetic activity. We will test the following specific hypotheses: 1) The hypotension associated with rapid hemorrhage results from activation of this peptidergic system and the resultant decrease in sympathetic nerve activity; 2) Cardiac afferent mechanisms initiate this depression of sympathetic outflow; (3) Other pressor systems (e.g., renin- angiotensin and vasopressin) are affected by and interact with this peptidergic depressor system; 4) Adrenal release of catecholamines is modulated by opioid peptides through a peripheral action. Since the effects of endogenous opioid peptides are affected by anesthetics, these studies will be performed with indwelling arterial and venous catheters, flow probes and nerve recording electrodes. Plasma and adrenal catecholamines will be measured by HPLC with electrochemical detection. The proposed studies are a natural continuation of our earlier work. They are directed toward an understanding of the role of this peptidergic system in modulation of sympathetic activity, and thus, cardiovascular function.
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