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)

Splanchnic and systemic hemodynamics in portal hypertensive rats during hemorrhage and blood volume restitution.

In portal hypertension the hemodynamic events after episodes of bleeding and blood transfusions may have important pathophysiological and therapeutic implications. The present study was designed to evaluate the effect of hemorrhage and blood restitution on splanchnic and systemic hemodynamics in a rat model of portal hypertension induced by portal vein constriction. In 16 portal hypertensive rats, sequential measurements of arterial and portal pressure were obtained during withdrawal and reinfusion of 15 ml X kg-1 body wt of blood. At the completion of the hemorrhage, a decrease of 16.9% +/- 2.6% in arterial pressure and 27.3% +/- 2.2% in portal pressure was observed. After blood reinfusion, arterial pressure returned to baseline values while portal pressure increased by 20.4% +/- 3.2% (p less than 0.01). This increase in portal pressure was not observed in 5 normal rats that were subjected to the same blood volume changes. Hemodynamic studies using a radioactive microsphere technique revealed that the withdrawal of 15 ml X kg-1 body wt of blood is followed by a decrease in portal venous inflow (6.4 +/- 0.4 vs. 10.4 +/- 0.6 ml X min-1 X 100 g-1 body wt in the control group, p less than 0.01). After blood volume restitution, the portal venous inflow returned to control values while the portal-collateral resistance increased significantly (2.06 +/- 0.13 vs. 1.67 +/- 0.07 mmHg X min X ml-1. 100 g, p less than 0.05). These results indicate that during hypovolemia there is a marked reduction in portal pressure because of a reduction in portal venous inflow. Blood volume restitution returns the portal venous inflow to control values. However, the portal pressure increases beyond control values because of an increase in portal-collateral resistance.