The objective of this application is to test the hypothesis that the renal renin-angiotensin system (Ang II) is as important as cardiac and arterial baroreceptor afferents in the stimulation of vasopressin (AVP) secretion and drinking in response to hypovolemia. The design of these studies employs comparisons of drinking and AVP responses induced by hypovolemia in conscious dogs, following selective removal of cardiac afferents, sinoaortic afferents or the subfornical organ (SFO). The techniques to be used include acute reversible blockade of cardiac nerves by intrapercardial infusion of procaine; chronic denervation of sinoaortic baroreceptors (SAD) or control of carotid sinus pressure following aortic baroreceptor denervation; and electrolytic ablation of the SFO which contains the central receptors activated by circulating Ang II to stimulate release of AVP and drinking in the dog. Hypovolemia will be induced by hemorrhage or acute reversible thoracic inferior vena caval constriction.
The specific aims will test the hypothesis that cardiac afferents are not essential for stimulation of drinking and AVP release in response to hemorrhage. Preliminary results indicate that acute cardiac nerve blockade does not alter drinking and AVP release in response to hemorrhage, in contrast to recent studies, and indicate a prominent role for arterial and/or Ang II-dependent mechanisms. The hypothesis that Ang II and carotid sinus baroreceptors are important mechanisms will be tested by comparing responses following SAD and/or SFO ablation to control responses with and without acute cardiac nerve blockade. Carotid sinus pressure will be controlled in some studies to confirm results based on SAD. Finally, the hypothesis that pressor responses to Ang II in the euvolemic state inhibit drinking AVP secretions will be tested during control of carotid sinus pressure or acute cardiac nerve blockade. These studies evaluate basic mechanisms which control intake and retention of water via AVP and are essential to understanding derrangements in volume regulation in pathologic states involving the heart and kidneys.
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