Angiotensin AT 2 receptors mediate vasodepressor response to footshock in rats : Role of kinins, nitric oxide and prostaglandins

Abstract

Footshocks increased mean arterial pressure and heart rate. Systemic administration of losartan, a specific angiotensin AT 1 receptor antagonist, not only inhibited the pressor response to footshocks, but also resulted in vasodepression. Administration of 1-[[4-(dimethylamino)3-methylphenyl]methyl]-5 (diphenylacetyl)-4,5,6,7-tetrahydro-1 H imidazol (4,5- c] pyridine-6-carboxilic acid, ditrifluoro acetatemonohydrate (PD 123319), a specific angiotensin AT 2 receptor antagonist, did not alter the hemodynamic response to footshocks. Simultaneous blockade of angiotensin AT 1 and AT 2 receptors by combined administration of losartan and PD 123319, eliminated the vasodepressor response to footshocks unmasked in losartan-pretreated rats. Saralasin, a non-specific angiotensin receptor antagonist, abolished the cardiovascular response to footshocks similarly like the losartan+PD 123319 treatment. Our data suggest that the vasodepressor response to footshocks in the presence of an angiotensin AT 1 receptor antagonist is triggered by activation of angiotensin AT 2 receptors. We studied the role of kinins, nitric oxide and prostaglandins in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan-treated rats was blunted by icatibant (HOE 140), N G-nitro- l-arginine-methyl ester ( l-NAME) or indomethacin, indicating that kinins, nitric oxide and prostaglandins appear to be involved in the pressure response to footshocks during angiotensin AT 1 receptor blockade.