ENHANCED CYCLOOXYGENASE-1 EXPRESSION WITHIN THE SUPERIOR MESENTERIC-ARTERY OF PORTAL HYPERTENSIVE RATS - ROLE IN THE HYPERDYNAMIC CIRCULATION

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to enhanced production of vasodilator substances. Enhanced vasodilati on and increased splanchnic blood flow contribute to the elevated port al pressure characteristic of PHT. The aim of this study was to determ ine whether cyclooxygenase (Cox) expression is altered in PHT vessels and whether chronic inhibition of this enzyme impacts on splanchnic bl ood flow in PHT. PHT was created in Sprague-Dawley rats by a partial p ortal vein ligation. Control animals were sham operated. Plasma 6-keto -PGF(1) alpha (prostaglandin F-1 alpha) levels were significantly elev ated in PHT after 2 days as compared with sham and remained elevated u p to day 15. Treatment with indomethacin (2 mg/kg ip daily for 15 days ) resulted in a significant decrease in 6-keto-PGF(1) alpha levels, wh ich was concomitant with a significant decrease in superior mesenteric artery blood flow (Qsma) after 15 days in PHT rats. Cox-I expression was differentially enhanced in the PHT superior mesenteric artery and thoracic aorta during the development and progression of PHT In contra st, Cox-II messenger RNA (mRNA) and protein expression was not detecte d in either of these vessels throughout the development of PHT These d ata suggest that PHT is associated with enhanced Cox-I expression with in the splanchnic vasculature concomitant with elevated plasma prostac yclin levels and a significant presser response to indomethacin in PHT animals. We conclude that enhanced Cox-I expression results in increa sed prostacyclin levels that partially contribute to the maintenance o f the hyperemia typical of PHT.