ACUTE AND CHRONIC CYCLOOXYGENASE BLOCKADE IN PORTAL-HYPERTENSIVE RATS- INFLUENCE ON NITRIC-OXIDE BIOSYNTHESIS

Background & Aims: Prostacyclin and nitric oxide have been involved in the hyperkinetic syndrome in portal hypertension. The aim of this stu dy was to investigate the relative contribution and possible interacti on between prostacyclin and NO in this circulatory abnormality. Method s: Portal vein-ligated and sham-operated rats received indomethacin an d vehicle either on a short-term (5 mg/kg subcutaneously) or long-term basis (5 mg . kg(-1). day(-1), continuous 7-day infusion with an osmo tic minipump). Measurements of arterial pressure and superior mesenter ic arterial flow (mL . min(-1). kg(-1), ultrasonic flow probe) were th en performed before and after N-G-nitro-L-arginine methyl ester (L-NAM E) injection (13 mg/kg intravenously). Results: Short-term or long-ter m indomethacin treatment had no effect in sham-operated rats but signi ficantly decreased mesenteric arterial flow in portal-hypertensive rat s. Mesenteric flow remained higher after long-term than after short-te rm indomethacin treatment (54.5 +/- 2 vs. 46.1 +/- 2; P = 0.01). This blunted response to long-term indomethacin treatment was associated wi th an enhanced response to L-NAME, shown by greater increments in arte rial pressure (29% +/- 3%) and mesenteric arterial resistance (209% +/ - 22%) in indomethacin-treated rats than in rats receiving vehicle (19 % +/- 2% and 130% +/- 20%; P < 0.05). Conclusions: Both prostacyclin a nd NO contributed to splanchnic hyperemia in portal-hypertensive rats. There was an enhanced release of NO after long-term prostacyclin inhi bition, suggesting that both vasodilatory systems interact, promoting splanchnic hyperemia in portal hypertension.