INVOLVEMENT OF ANGIOTENSIN RECEPTOR SUBTYPES IN OSMOTICALLY INDUCED RELEASE OF VASOPRESSIN

We have previously shown that AT(1) and AT(2) angiotensin II (Ang II) receptors mediate the release of arginine vasopressin (AVP) to central injections of Ang II. In this study we have tested the hypothesis tha t Ang II, acting at AT(1) and AT(2) receptors in the brain, is involve d in mediating osmotically stimulated AVP release. Adult Sprague-Dawle y rats were fitted with intraventricular (i.v.t.) cannulas and cathete rs in the carotid artery and the femoral vein. Intraventricular inject ions of Ang II receptor antagonists specific to different subtypes of the receptor (AT(1) and AT(2)) were given before a 30 min infusion of hypertonic (2.5 M) saline. Arterial blood samples were collected 5 min before and at two time points after(+15 min and +30 min) beginning th e saline infusion. We found that both losartan (AT(1) specific) and CG P42112A (AT(2) specific) significantly reduced osmotically induced rel ease of AVP. PD123319 (AT(2) specific) had no effect of osmotically st imulated AVP release. A combined treatment of losartan +PD123319 was n o more effective than losartan in blocking the AVP response. Since los artan was the most rapid and effective antagonist of osmotically stimu lated AVP release, we conclude that AT(1) receptors are directly invol ved in the response. However, but since CGP42112A was also an effectiv e antagonist and since, AT(2) receptors are located at sites distant f rom the hypothalamus, such as the locus ceruleus, they may also contri bute to this response. We conclude that brain Ang II receptors are inv olved in osmotically stimulated AVP release.