Losartan reduces constrictor responses to endothelin-1 and the thromboxane A2 analogue in aortic rings from spontaneously hypertensive rats:: role of nitric oxide

Objective Our study was designed to investigate whether angiotensin II subtype 1 (AT(1)) receptors are involved in the constrictor responses evoked by endothelin-1 and the thromboxane A(2) analogue U46619 in aortic rings from spontaneously hypertensive rats (SHR), by studying the effect of the AT(1) receptor antagonist losartan. In addition, since nitric oxide seems to participate in the mechanism of action of losartan, we studied the effect of the nitric oxide synthesis inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), on the action of losartan. Materials and methods Dose-response curves of either endothelin-1 (10(-10) to 10(-7) mol/l) or U46619 (10(-10) to 10(-6) mol/l) were studied in the presence or absence of losartan (10(-5) mol/l) in aortic rings from SHR. Likewise, similar experiments were done in aortic rings pretreated with the nitric oxide synthesis inhibitor, L-NAME (10(-4) mol/l). Results Pre-incubation with losartan significantly reduced the contractile response to endothelin-1 compared with control rings, without modifying the value represented by 50% of the maximal response (pD(2)). The concentration-response curve to U46619 was shifted to the right in the presence of losartan, reducing the pD(2) compared with control rings. The presence of captopril (10(-5) mol/l) in the incubation media did not alter the response to either endothelin-1 or U46619. The diminished response to both endothelin-1 and U46619 in the presence of losartan was reversed in L-NAME-pretreated rings. Conclusions Angiotensin II seems to participate in the vasoconstriction induced by both endothelin-1 and the thromboxane A(2) analogue through the stimulation of AT(1) receptors in SHR aortic rings, because losartan inhibited this effect. Moreover, nitric oxide appears to be involved in this action of losartan. (C) Rapid Science Publishers ISSN 0263-6352.