CARDIOVASCULAR DETERMINANTS OF CATECHOLAMINE RELEASE

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Evaluation of the role of Prostaglandin E2 (PGE2) delivered systemically as intravenously infused PGE2 and centrally by ventriculo-cisternal perfusion in controlling centrally mediated, Angiotensin II dependent, reflexly excited adrenal medullary catecholamine release in acutely anephric dogs are our goals for the next grant period. In anesthetized, heparinized dogs following acute nephrectomy and placement of adreno-femoral shunts and aortic cannulae we will study the dose responsiveness of intravenous PGE2's ability to restore normal adrenal reflex catecholamine release elicited by acute hemorrhage. With an appropriate sub-systemic threshold dose of PGE2 derived from that data, we then will perfuse ventriculo-cisternal PGE2 in anesthetized acutely anephric dogs with threshold quantities of PGE2 on reflex catecholamine release following hemorrhage. Finally, we will infuse, ventriculo-cisternally, Angiotensin II and PGE2 concomitantly to define the central effect of PGE2 on Angiotensin II responsiveness. Ventriculo-cisternally perfused PGE2 will be evaluated in two different ways; in one set of experiments, I.V. Angiotensin and ventriculo-cisternally perfused PGE2 will both be given and in another set of experiments, PGE2 and Angiotensin II will be given concominantly in the ventriculo-cisternal perfusion circuit. Understanding the neuro-hormonal control reflex catecholamine release is one long-term objective; another related goal is understanding whether or not renal hormones, specifically renin and the Angiotensin II generated under its infuence and PGE2, are needed to support central nervous system reflex activity. Such physiologic insights will, we hope, help us understand disordered central nervous system mechanisms involved in clinical hypertension.