Angiotensin AT2 receptors mediate vasodepressor response to footshock in rats -: Role of kinins, nitric oxide and prostaglandins

Footshocks increased mean arterial pressure and heart rate. Systemic administration of losartan, a specific angiotensin AT(1) receptor antagonist, not only inhibited the presser 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 acetate-monohydrate (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. (C) 2000 Elsevier Science B.V. All rights reserved.