RESPONSES TO ANGIOTENSIN PEPTIDES ARE MEDIATED BY AT(1) RECEPTORS IN THE RAT

The effects of the angiotensin AT(1) and AT(2) receptor antagonists ca ndesartan and PD-123,319 on hemodynamic responses to angiotensin pepti des were investigated in the anesthetized rat. Injections of angiotens in II and III caused dose-related increases in systemic arterial and i n hindquarters perfusion pressure that were reduced in an insurmountab le manner by candesartan. Presser responses to angiotensin IV were als o attenuated, and a vasodepressor or vasodilator response to the angio tensin peptides was not unmasked by the AT(1) receptor antagonists can desartan or losartan. The AT(2) receptor antagonist PD123,319 had no s ignificant effect on increases in systemic arterial and hindquarters p erfusion pressure in response to the angiotensin peptides. Presser res ponses to angiotensin peptides were not altered by adrenergic nerve te rminal and alpha-receptor blocking agents or by the cyclooxygenase inh ibitor sodium meclofenamate but were increased by an inhibitor of nitr ic oxide synthase. The present results suggest that presser responses to the angiotensin peptides are mediated by the activation of AT(1) re ceptors and that AT(2) receptors, the adrenergic system, or cyclooxyge nase products do not appear to modulate hemodynamic responses to the a ngiotensin peptides in the anesthetized rat.