Hypersensitivity of mesenteric veins to 5‐hydroxytryptamine‐ and ketanserin‐induced reduction of portal pressure in portal hypertensive rats

Abstract

1 Isolated superior mesenteric veins from portal hypertensive rats were 3 to 10 times more sensitive to 5-hydroxytryptamine (5-HT) and 3 times less sensitive to (-)-noradrenaline than veins from sham-operated rats. The sensitivity to vasopressin did not differ in the 2 groups. 2 Ketanserin competitively antagonized the effects of 5-HT in superior mesenteric veins and portal veins with high affinity (K_B values 0.1-0.3 nM), as expected for 5-HT₂-receptors. The affinity of ketanserin for 5-HT₂-receptors was similar in veins from normal, sham-operated or portal-hypertensive rats. 3 Intraportal injections of low doses of 5-HT caused increases in portal pressure which were more pronounced in portal hypertensive rats than in sham-operated rats and were blocked by 0.3 mg kg⁻¹ ketanserin in both groups. Ketanserin 0.3 mg kg⁻¹ did not block the portal pressor response to (-)-noradrenaline in either group of rats. 4 In portal hypertensive rats but not in sham-operated rats, 0.3 mg kg⁻¹ ketanserin caused decreases in portal pressure, portal flow and cardiac output, as estimated by radioactive microspheres. 5 The reduction in portal pressure caused by ketanserin was due mainly to a decrease in portal venous inflow secondary to a decreased cardiac output. The reduction in cardiac output, which was observed only in the portal hypertensive rats but not in sham-operated rats, is consistent with venous dilatation and pooling of blood in the portal venous system. The venous pooling could be secondary to the blockade of 5-HT₂-receptors in the portal venous system. It is proposed that ketanserin should be explored for the treatment of patients with portal hypertension.