ICI 169,369 selectively blocks 5-hydroxytryptamine2 receptors and lowers portal pressure in portal hypertensive rats

The contractile effects of 5-hydroxytryptamine on isolated portal veins and superior mesenteric veins of portal hypertensive rats (portal vein constricted) were antagonized competitively by ICI 169,369. The equilibrium dissociation constant of 1-3 nM for ICI 169,369, estimated in the veins, agrees with affinity estimates for arterial 5-hydroxytryptamine2 receptors. The receptors of portal veins of sham-operated rats had the same affinity for ICI 169,369 as the receptors of portal hypertensive rats. The systemic administration of ICI 169,369 to portal hypertensive rats decreased portal pressure from 13.0 +/- 0.4 to 11.3 +/- 0.5 mmHg (p less than 0.01) but did not affect arterial pressure. ICI 169,369 induced nonsignificant changes in both portal venous inflow and portocollateral resistance, as estimated by the radioactive microsphere technique. It is estimated that the combined changes in portal flow and resistance could explain the decrease in portal pressure. The results are consistent with an involvement of 5-hydroxytryptamine, acting through 5-hydroxytryptamine2 receptors, in prehepatic portal hypertension.