CARDIOVASCULAR CONSEQUENCES OF MICROINJECTION OF VASOPRESSIN AND ANGIOTENSIN-II IN THE AREA POSTREMA

Microinjection of angiotensin II (ANG II) into the area postrema (AP) of urethan-anesthetized male Sprague-Dawley rats elicited statisticall y significant increases in mean arterial blood pressure at doses rangi ng from 10 pg to 500 ng (10 pg, mean +/- SE, 10.8 +/- 1.1 mmHg, P < 0. 001; 250 ng, 15.2 +/- 2.6 mmHg, P < 0.001). Heart rate was also signif icantly increased at doses >10 pg, although these increases were not d ose dependent. Systemic administration of losartan (Dup-753), an AT1 a ntagonist, was able to significantly reduce the pressor response to 25 0 ng ANG (post-losartan: 81.9 +/- 9.5% reduction in blood pressure res ponse, P < 0.0001), whereas PD123319, an AT2 antagonist, was without s ignificant effect (P > 0.1). Microinjection of vasopressin (VP) (10 pg -500 ng) into the AP also resulted in statistically significant increa ses in blood pressure at doses ranging from 10 to 100 pg (10 pg, 7.0 /- 1.5 mmHg, P < 0.05) and 100-500 ng (250 ng, 12.2 +/- 1.8 mmHg, P < 0.0001). Small but significant changes in heart rate were observed onl y at 100 pg and 100 ng. Systemic administration of a V1 antagonist sig nificantly attenuated the increases in blood pressure in response to 5 0, 100, and 250 ng VP (250 ng, post-V1 antagonist: 66.4 +/- 8.6% reduc tion in blood pressure response, P < 0.001), whereas [desamino,D-Arg8] vasopressin (DDAVP), a V2 agonist, had a depressor effect when microin jected directly into the AP (250 ng, -9.9 +/- 1.6 mmHg, P < 0.005). Ra dioimmunoassay of plasma VP levels verified that microinjection of thi s peptide into the AP did not result in increased circulating VP conce ntrations (before microinjection: 32.2 +/- 3.8 pg/ml; after microinjec tion: 37.0 +/- 5.2 pg/ml, P > 0.1), suggesting that the pressor action s are not due to leakage of VP into the circulation. These results sup port a functional role for the AT1 and V1 receptors within the AP in c ardiovascular regulation. They also suggest the possibility of central ly localized V2 receptors involved in cardiovascular homeostasis.