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 that Ang II, acting at AT(1) and AT(2) receptors in the brain, is involved in mediating osmotically stimulated AVP release. Adult Sprague-Dawley rats were fitted with intraventricular (i.v.t.) cannulas and catheters in the carotid artery and the femoral vein. Intraventricular injections 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 the saline infusion. We found that both losartan (AT(1) specific) and CGP42112A (AT(2) specific) significantly reduced osmotically induced release of AVP. PD123319 (AT(2) specific) had no effect of osmotically stimulated AVP release. A combined treatment of losartan +PD123319 was no more effective than losartan in blocking the AVP response. Since losartan was the most rapid and effective antagonist of osmotically stimulated AVP release, we conclude that AT(1) receptors are directly involved in the response. However, but since CGP42112A was also an effective antagonist and since, AT(2) receptors are located at sites distant from the hypothalamus, such as the locus ceruleus, they may also contribute to this response. We conclude that brain Ang II receptors are involved in osmotically stimulated AVP release.