MICROINFUSION OF AMINOPEPTIDASE-M INTO THE PARAVENTRICULAR NUCLEUS OFTHE HYPOTHALAMUS IN NORMOTENSIVE AND HYPERTENSIVE RATS

Normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (S HR) received aminopeptidase M (AmM) delivered into the paraventricular nucleus of the hypothalamus (PVN). Resulting changes in blood pressur e were recorded in both anesthetized and alert animals. The findings i ndicate significant dose-determined decreases in blood pressure in mem bers of both strains with SHR more responsive than WKY rats. The respe ctive drops in blood pressure for members within each strain were equi valent for the anesthetized and alert conditions. Pretreatment with th e specific angiotensin receptor antagonist, sarthran, [Sar(1),Thr(8)]A ngII, into the PVN greatly diminished these responses, suggesting the involvement of the brain angiotensin system. Additionally, a sympathet ic nervous system blocker, hexamethonium, and the arginine vasopressin antagonist, Pmp(1),O-Me-Tyr(2)-[Arg]vasopressin, were peripherally ad ministered to assess the potential contributions of these systems to c ardiovascular regulation by the brain angiotensin system. The use of t hese blockers, individually and combined, attenuated responsiveness to infusion of AmM into the PVN. We conclude that AmM can act as a hypot ensive agent in both SHR and WKY rats, and that this decrease in blood pressure is at feast partially mediated via the brain angiotensin sys tem although other systems may play a role.