Angiotensin III depressor action in the conscious rabbit is blocked by losartan but not PD 123319

Vasodilator and vasodepressor properties of angiotensins have been reported , and mediation by prostaglandins or nitric oxide has been proposed. Other studies indicate that angiotensin AT(2) receptors might mediate a depressor or nitric oxide has been proposed. Other studies indicate that angiotensin AT(2) receptors might mediate a depressor action, and the present study wa s designed to delineate and explore this possibility in a conscious rabbit model. Large intravenous boluses of angiotensin III (15 nmol/kg) produced a predictable pressor peak (83+/-4 mm Hg) followed by a depressor phase (20/-3 mm Hg), whereas equipressor doses of angiotensin II were less effective at producing depressor responses. Angiotensin-(1-7) did not exert a depres sor action, and the reduced potency of angiotensin IV (relative to angioten sin III) was similar for both the presser and depressor phases (approximate to 100-fold). It is clear that specific angiotensin IV or angiotensin-(1-7 ) receptors do not mediate depressor effects in this model. The AT(1) antag onist losartan (1 mg/kg) blocked both the presser and depressor components of the angiotensin III response, whereas the AT(2) antagonist PD 123319 (35 mg/kg) had no effect on either element of the response. The data obtained with the angiotensin receptor subtype-selective compounds, losartan and PD 123319, suggest that the depressor action is an AT(1)-mediated effect and g ive no indication that AT(2) receptors could be involved. Paradoxically, th e greater potency of angiotensin III as a vasodepressor belies the conclusi on that the response is AT(1)-mediated, because AT(1) receptors have a grea ter affinity for angiotensin II versus angiotensin III.