Hypersensitivity of mesenteric veins to 5-hydroxytryptamine- and ketanserin-induced reduction of portal pressure in portal hypertensive rats.
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. Ketanserin competitively antagonized the effects of 5-HT in superior mesenteric veins and portal veins with high affinity (KB 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. 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. 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. 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.
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D014690:Venous Pressure / Q000187:drug effects
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D009638:Norepinephrine