Brain AT 2 receptor mediate vasodepressor response to footshocks: Role of kinins and nitric oxide

Abstract

In the present study the role of brain AT 2 receptor in the cardiovascular response to stress was investigated in conscious rats. Footshock-stress increased mean arterial pressure (MAP) and heart rate ( p < 0.0001). Intracerebroventricular (i.c.v.) administration of losartan (100 μg/5 μl), a specific angiotensin AT 1 receptor antagonist, not only attenuated the pressor response to footshocks, but also resulted in a consistent vasodepressor response (−10 mmHg, p < 0.02). Meanwhile, heart rate response was not altered. Given alone, PD 123319 (3 μg/5 μl, i.c.v.), a specific angiotensin AT 2 receptor antagonist, did not alter the hemody-namic response to footshocks. However, simultaneous block of brain AT 1 and AT 2 receptors by combined administration of losartan and PD 12319, eliminated the vasodepressor response unmasked after footshocks in rats i.c.v.-pretreated with losartan alone. In addition, we studied the role of brain kinins and nitric oxide (NO) in the vasodepressor response observed after footshocks in losartan i.c.v.-treated rats. Intracerebroventricular administration of icatibant (20 pmol/5 μl), a selective B 2 receptor antagonist, or N G-nitro- l-arginine methyl ester (100 μg/5 μl), a selective NO-synthase inhibitor, abolished the vasodepressor response to footshocks in losartan-treated rats. Our data suggest that the vasodepressor response to footshocks in the presence of AT 1 antagonist is triggered by activation of AT 2 receptor. Brain NO and kinins appear to contribute in this effect.