Responses to angiotensin peptides are mediated by AT1 receptors in the rat

The effects of the angiotensin AT(1) and AT(2) receptor antagonists candesartan and PD-123,319 on hemodynamic responses to angiotensin peptides were investigated in the anesthetized rat. Injections of angiotensin II and III caused dose-related increases in systemic arterial and in hindquarters perfusion pressure that were reduced in an insurmountable manner by candesartan. Presser responses to angiotensin IV were also attenuated, and a vasodepressor or vasodilator response to the angiotensin peptides was not unmasked by the AT(1) receptor antagonists candesartan or losartan. The AT(2) receptor antagonist PD123,319 had no significant effect on increases in systemic arterial and hindquarters perfusion pressure in response to the angiotensin peptides. Presser responses to angiotensin peptides were not altered by adrenergic nerve terminal and alpha-receptor blocking agents or by the cyclooxygenase inhibitor sodium meclofenamate but were increased by an inhibitor of nitric oxide synthase. The present results suggest that presser responses to the angiotensin peptides are mediated by the activation of AT(1) receptors and that AT(2) receptors, the adrenergic system, or cyclooxygenase products do not appear to modulate hemodynamic responses to the angiotensin peptides in the anesthetized rat.