DURATION OF ACUTE AND SUBACUTE CENTRAL SAR(1)-ILE(8)-ANGIOTENSIN II ANTAGONISM OF THE CENTRAL ANGIOTENSIN II AND III - INDUCED PRESSOR RESPONSE IN NORMOTENSIVE MALE RATS

Research directed toward the therapeutic control of essential hypertension has revealed the involvement of the renin-angiotensin-system in this regulatory malfunction. Elevations in circulating angiotensin II or III cause peripheral vasoconstriction, inhibition of reflex vasodilation, and stimulate the sympathetic nervous system. Thus blockade of the renin-angiotensin-system has been shown to be useful in the control of hypertension.;The third experiment employed acute administration of Sar('1)-Ile('8)-AII or a control injection of artificial CSF followed at 10, 30, 50, and 70 minutes by bolus injections of AII or AIII. Both angiotensins induced pressor responses which could be blocked by the sarcosine antagonist through the 30 minute injection and the patterns of pressor responses were equivalent for AII and AIII.;In a final experiment, Sar('1)-Ile('8)-AII or CSF was infused into the lateral ventricle by an osmotic mini pump for 24 hours. Central AII or AIII bolus injections followed at the intervals indicated above. The results evidenced no difference between AII and AIII. The blockade by the sarcosine antagonist lasted through the 50 minute injection which was slightly longer than the acute blockade. The effect of the acute and subacute (24 hour) Sar('1)-Ile('8)-AII administration was reversible within the 70 minute test period. The results suggest that the duration of the antagonist administration was not a significant factor in the duration of the pressor blockade to AII and AIII.;This investigation focused on the blockade of central receptors responsible for monitoring circulating levels of angiotensin with a centrally administered antagonist, Sar('1)-Ile('8)-AII. This was accomplished by the delivery of these compounds into the brain lateral ventricles via a chronic cannula. In the first and second experiments dose response curves were generated in order to select the dosages of AII, AIII, and Sar('1)-Ile('8)-AII to be used in the subsequent experiments.