Comparison of the hemodynamic responses to ketanserin and prazosin in portal hypertensive rats

Ketanserin, a serotonin antagonist, is effective in lowering portal pressure in a rat model of portal hypertension. As ketanserin has alpha 1-adrenoceptor-blocking properties in addition to its serotonin-blocking effects, we sought to define further the mechanism of ketanserin's portal pressure-lowering effect. We attempted to determine whether the portal pressure-reducing effect of ketanserin was due to the unspecific effect of arterial blood pressure reduction mediated by alpha 1-adrenoceptor blockade or to serotonin receptor-blocking properties of ketanserin. The hemodynamic action of prazosin and alpha 1-adrenoceptor antagonist and ketanserin were compared in portal hypertensive rats in which the arterial pressure was equally reduced by both agents. The portal pressure was significantly lower in the ketanserin-treated group (11.3 +/- 0.4 mm Hg) when compared to the saline-treated group (13.6 +/- 0.7 mm Hg). The portal pressure was not significantly lower in the prazosin-treated group when compared to the saline-treated group (12.3 +/- 0.5 vs. 13.6 +/- 0.7 mm Hg, respectively). The same relationship held true for portal venous inflow and cardiac output. For each measurement, results in the ketanserin group were significantly lower when compared to the saline-treated group. These data in the prazosin-treated group were similar to data in the saline-treated group. The differences between the effect of ketanserin and prazosin were obtained despite similar blood pressure decreases. Ketanserin produced an 18% decrease and prazosin a 14% decrease in blood pressure when values were compared to their preinjection baselines.(ABSTRACT TRUNCATED AT 250 WORDS)