INCREASED EXPRESSION OF ENDOTHELIN RECEPTORS IN THE VASCULATURE OF PORTAL HYPERTENSIVE RATS - ROLE IN SPLANCHNIC HEMODYNAMICS

Portal hypertension (PHT) is characterized by increased portal pressur e caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and spe cific ET receptors in maintaining the vasculopathy of PHT. PHT was cre ated in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated, ET receptor expression was determined in the superior mesenteric artery of sham and PI-IT rats by in situ autor adiography, radioligand binding analysis, and reverse-transcription po lymerase chain reactions (RT-PCR), The presser response to ET-1 was de termined in vitro using isolated vascular rings and in vivo by measuri ng mean arterial pressure, splanchnic blood flow, and portal venous pr essure following treatment with ET and selective ET receptor antagonis ts. The presser response to ET in vitro was significantly enhanced in PI-IT concomitant with increased ET-A and ET-B receptor expression. Th ere was a significant increase in the peak presser response to ET (10 mu g/kg intravenously) in portal hypertensive rats without any signifi cant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 mu g/kg in travenously), In contrast, ET-B receptor blockade with IRL-1038 (200 m u g/kg intravenously) preferentially decreased splanchnic blood flow a nd portal venous pressure in portal hypertensive rats. These data sugg est that enhanced ET-B receptor expression in portal hypertensive vess els contributes to the maintenance of elevated portal pressure in thes e animals.