EVIDENCE AGAINST A ROLE FOR INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE HYPERDYNAMIC CIRCULATION OF PORTAL-HYPERTENSIVE RATS

Background/Aims: Excessive nitric oxide biosynthesis caused by express ion of inducible NO synthase has been implicated in the hyperdynamic c irculation of portal hypertension. The aim of the study was to investi gate whether inducible NO synthase is expressed in portal hypertension and accounts for the hyperdynamic circulation. Methods: In study 1, N O synthase activities were measured by the conversion of L-arginine to citrulline in tissues from portal-hypertensive, cirrhotic, and sham-o perated rats and from normal rats pretreated with endotoxin and after long-term administration of dexamethasone, which inhibits the expressi on of inducible NO synthase. In study 2, systemic and splanchnic hemod ynamics (radiolabeled microspheres) and gastric blood flow (hydrogen g as clearance and reflectance spectrophotometry) were measured in porta l-hypertensive rats after long-term administration of dexamethasone (0 .25 mg . kg(-1) . day(-1)) or vehicle. Results: In study 1, constituti ve and inducible NO synthase activities in portal-hypertensive or cirr hotic rats were similar to those observed in sham-operated rats. The s ignificant increase in the inducible activity observed after endotoxin injection was prevented when rats received long-term treatment with d examethasone. In study 2, cardiac index, portal-pressure, portal venou s inflow, and gastric blood flow were similar in dexamethasone- or veh icle-treated portal-hypertensive vats. Conclusions: These results do n ot support a role for an increased expression of the inducible NO synt hase in the hyperdynamic circulation of portal hypertension.