ENHANCED G-PROTEIN-INDUCED RELAXATION IN PORTAL HYPERTENSIVE RATS - ROLE OF NITRIC-OXIDE

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. The reasons for the decreased resistance include an increased responsiveness to a vasodil ator substance. Because the activation of an inhibitory guanine nucleo tide regulatory (Gi) protein can result in endothelium-dependent relax ation, we tested the hypothesis that exaggerated Gi-protein induced re laxation via a nitric oxide (NO)-dependent pathway partly reflects the enhanced Gi-protein expression in PHT vessels. PHT was created in Spr ague-Dawley rats by a partial portal-vein ligation, Control animals we re sham operated. Using isolated vascular rings in the absence or pres ence of an intact endothelium, N-G-nitro-L-arginine methyl ester (L-NA ME), and pertussis toxin, dose response relationships for sodium fluor ide (NaF; range, 0.1-4 mmol/L), a Gi protein activator, were determine d in a cumulative manner. Gi-protein expression was determined by West ern blotting. NaF caused a dose-dependent relaxation in both sham and portal hypertensive pre-contracted vessels, an effect that was signifi cantly inhibited by pertussis toxin, endothelial denudation, and L-NAM E. Concentrations of NaF greater than 4 mmol/L caused contractions, an effect that was unaffected by L-NAME. The NaF-induced relaxation resp onse was significantly greater in PHT vessels as compared with sham co ncomitant with increased Gi-protein expression in PHT vessels. These d ata suggest that the enhanced endothelial Gi-protein-induced relaxatio n in PHT vessels may partly reflect enhanced expression of Gi-proteins in PHT vessels and may, thus, represent an important mechanism for ex aggerated NO-dependent relaxation in the PHT vasculature.