ANGIOTENSIN-II-INDUCED VASOPRESSIN RELEASE IS MEDIATED THROUGH ALPHA-1-ADRENOCEPTORS AND ANGIOTENSIN-II AT1 RECEPTORS IN THE SUPRAOPTIC NUCLEUS

The central actions of angiotensin II (ANG II) include the release of vasopressin (AVP) from the supraoptic nucleus (SON) via the pituitary gland into the blood. In conscious rats, we investigated whether catec holamines in the SON are involved in this release process. It was foun d that i.c.v. injections of ANG II (100 ng) selectively increased the release of norepinephrine (NA) from the SON. Like the ANG II i.c.v.-in duced AVP release, this effect was prevented by i.c.v. pretreatment wi th the ANG II AT1 receptor antagonist, losartan (5 mug). The alpha-1 a drenoceptor antagonist, prazosin (0.7 nmol), injected bilaterally into the SON, significantly reduced the ANG II 100-ng i.c.v.-induced AVP r elease. Pretreatment with the alpha-2, beta-1 and beta-2 adrenoceptor antagonists, idazoxan, atenolol and ICI 118551, respectively, had no e ffect. Injections of NA into the SON increased plasma AVP at doses up to 10 nmol but not at higher doses (30-100 nmol). The effects of NA we re mimicked by the alpha-1 adrenoceptor agonist, methoxamine (1-5 nmol ). Bilateral pretreatment of the SON with losartan (5 mug) markedly in hibited the i.c.v. ANG II 100 ng-induced AVP release. The increase in AVP release after ANG II injections into the SON was also inhibited by losartan pretreatment into the SON, whereas prazosin had no effect. T hese results demonstrate that the ANG II-induced release of AVP is ini tiated through periventricular ANG II AT1 receptors and involves posts ynaptic alpha-1 adrenoceptor stimulation in the SON. In addition, ANG II AT1 receptors in the SON can contribute to AVP release after perive ntricular ANG II receptor stimulation.