AMINOGUANIDINE REVERSES AORTIC HYPOREACTIVITY TO NORADRENALINE IN PORTAL VEIN-LIGATED RATS

To evaluate the role of the inducible and endothelial constitutive nit ric oxide synthase in vascular hyporeactivity to vasopressors in porta l hypertension, in vitro experiments were performed on intact and endo thelium-denuded isolated thoracic aortic rings from portal vein-ligate d and sham-operated rats in control conditions, in the presence of ami noguanidine alone, considered to be a selective inhibitor of the induc ible nitric oxide synthase, and of aminoguanidine and the nonselective nitric oxide synthase inhibitor N-G-nitro-L-arginine. In control cond itions, hyporeactivity to noradrenaline was observed in both rings wit h and without endothelium from portal hypertensive versus sham-operate d rats. In the rings with endothelium, aminoguanidine reverted this hy poreactivity in portal hypertensive rats. N-G-Nitro-L-arginine caused an additional shift to the left of the concentration-response curves t o noradrenaline in portal hypertensive and a similar shift in sham-ope rated rats, In the endothelium-denuded rings, aminoguanidine caused no significant changes in portal hypertensive rats, whereas a significan t shift to the right in the sham-operated rats was noted, however simi lar as the shift in the time controls not preincubated with aminoguani dine. No significant further changes were observed after preincubation with the two inhibitors. The endothelium-dependent relaxations to ace tylcholine were attenuated in portal hypertensive versus sham-operated rats; addition of aminoguanidine shifted the relaxation curves to the left in portal hypertensive but not in sham-operated rats. These resu lts provide indirect evidence for an increased activity of the inducib le nitric oxide synthase in the intact aortic rings but not in the end othelium-denuded rings from portal vein-ligated rats, where other fact ors seem to be responsible for the observed hyporeactivity to noradren aline. The endothelial constitutive nitric oxide synthase in rings fro m portal vein-ligated rats shows a reduced activity which is alleviate d after inhibition of the inducible enzyme by aminoguanidine. (C) 1997 Elsevier Science B.V.