ROLE OF NITRIC-OXIDE IN HYPOREACTIVITY TO NORADRENALINE OF ISOLATED AORTIC RINGS IN PORTAL HYPERTENSIVE RATS

To test the hypothesis that induction of nitric oxide synthase causes systemic vascular hyporesponsiveness to vasopressors in portal hyperte nsion, we performed in vitro experiments on isolated thoracic aortic r ings from partial portal vein ligated or sham operated rats at 3 weeks postoperatively. The concentration-response curves to noradrenaline o f intact and endothelium-denuded aortic rings from portal hypertensive rats were significantly shifted to the right as compared to those fro m sham operated animals. Maximal contractions did not significantly di ffer. Addition of N-G-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, shifted the curves to the left in both sham operated and portal hypertensive rats, so that in intact rings, the concentrati ons of noradrenaline producing half-maximal response did not significa ntly differ any more between sham operated and portal vein ligated rat s. In endothelium-denuded rings, a hyporeactivity to noradrenaline per sisted in portal vein ligated rats. Furthermore, N-G-nitro-L-arginine induced an additional significant increase in the maximal response to noradrenaline in sham operated as compared to portal hypertensive rats . The endothelium-dependent relaxations to acetylcholine were attenuat ed in portal hypertensive rats as compared to sham operated animals. F rom these results, it can be concluded that increased nitric oxide pro duction in the vascular wall of thoracic aorta of portal hypertensive rats is involved in their hyporesponsiveness to noradrenaline. Our fin dings in endothelium-denuded rings indicate the involvement of the ind ucible nitric oxide synthase in the smooth muscle layer. Involvement o f an inducible nitric oxide synthase in the endothelium cannot be excl uded. The endothelial constitutive nitric oxide synthase, however, see ms to be suppressed in portal vein ligated rats.