EFFECTS OF BLOCKADE OF AT1-RECEPTORS AND AT2-RECEPTORS IN BRAIN ON THE CENTRAL ANGIOTENSIN-II PRESSOR-RESPONSE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

Intracerebroventricular (i.c.v.) administration of angiotensin II (ANG II) increases vascular resistance and arterial pressure by increasing the activity in the sympathetic nervous system (SNS-component) and se cretion of vasopressin (VP-component). This study examined the role of AT1 and AT2 receptors in brain in mediating the exaggerated central c ardiovascular effects of ANG II in conscious, adult (10 weeks) spontan eously hypertensive rats (SHR). Mean arterial pressure, heart rate and renal blood flow responses to intraventricular injection of ANG II (1 00 ng in 5 mul) were determined 10 min after intraventricular administ ration of the AT1 receptor antagonist losartan alone (1.0, 2.5, 5.0, 1 0.0 mug), the AT2 receptor ligand PD 123319 alone (3.5 x [10(-6), 10(- 4), 10(-2), 10(0)] mug), or both ligands in combination. In control ra ts, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P < 0.05), while intraventricul ar injection of PD 123319 was ineffective. Likewise, when the SNS- and VP-components were studied individually by preventing the VP-componen t with a V1 receptor antagonist (i.v.) or the SNS-component with chlor isondamine (i.v.), losartan (i.c.v.) prevented both components, while PD 123319 (i.c.v.) was without affect. In addition, doses of losartan, combined with 3.5 mug PD 123319, were no more effective in preventing the pressor or renal vascular resistance responses than losartan, adm inistered alone, suggesting that the VP- and SNS-components of the pre ssor response to ANG II (i.c.v.) are mediated primarily by AT1 recepto rs in brain in conscious spontaneously hypertensive rats. In contrast activation of AT2 reception did not appear to be involved in either pr essor component.