ENHANCED NITRIC-OXIDE SYNTHASE ACTIVITY IN PORTAL HYPERTENSIVE RABBITS

Portal hypertension (PHT) is characterized by splanchnic hyperemia cau sed by a reduction in mesenteric vascular resistance. Mediators of thi s hyperemia include nitric oxide (NO), This is based on several report s indicating a marked splanchnic hyporesponsiveness in PHT to vasocons trictor stimuli, both in vitro and in vivo, and a subsequent reversal using specific inhibitors of NO synthase (NOS). The objective of this study was to determine directly if the generation of NO is altered in PHT vasculature. Thus, we compared NOS activity in the hyperemic vascu lature of normal rabbits and rabbits with PHT (after undergoing partia l portal vein ligation). Nicotinamide adenine dinucleotide phosphate d iaphorase staining indicated the presence of NOS within the vascular e ndothelium. Ca2+-dependent NOS activity was significantly increased (P < .05) in PHT particulate fractions from the superior mesenteric arte ry and thoracic aorta, but not from the portal vein, There was no chan ge in NOS activity within the cytosolic fractions, Arterial wall cycli c guanosine monophosphate (cGMP) levels and plasma nitrite levels were both significantly increased in PHT. These results show enhanced NOS activity in PHT hyperemic vessels concurrent with increased tissue cGM P levels. We conclude that enhanced NO synthesis contributes to the hy perdynamic circulation of PHT.