THE HEMODYNAMIC-EFFECTS OF AT-112, AN ANALOG OF KETANSERIN, IN PORTALHYPERTENSIVE RATS

A serotonin mechanism has been reported to contribute to the hyperdyna mic circulation of portal hypertension. Different studies have demonst rated that serotonin antagonists decrease portal pressure in portal hy pertensive patients and animals. The present study was undertaken to i nvestigate the effect of AT-112, an analog of ketanserin, on portal hy pertension induced by partial portal vein ligation in rats. Since keta nserin is known to possess alpha(1)-adrenergic antagonistic activity, the effect of AT-112 was compared to that of prazosin. A single dose ( prazosin 4.2 mu g/kg, AT-112 I mg/kg) was chosen to produce a similar hypotensive effect (-20 +/- 4% for prazosin and -24 +/- 4% for AT-112) , At this dose, prazosin significantly decreased total peripheral resi stance whereas AT-112 significantly decreased cardiac index and heart rate, Both agents significantly decreased tile portal tributary blood flow and portal pressure. In rats receiving AT-112, a significant corr elation was found between the magnitudes of decrease in cardiac index and the decrease in portal tributary blood flow, We also found that th e magnitude of reduction in portal pressure was greater following AT-1 12 administration, This study suggested that AT-112 may have more bene ficial hemodynamic effects than prazosin in portal hypertensive rats. Our results provide further support for the serotonergic mechanism in the pathogenesis of hyperdynamic circulation in portal hypertension.