Blood Pressure, 5-OH Indoleacetic Acid, and Vanilmandelic Acid Excretion and Blood Platelet Aggregation in Hypertensive Patients Treated with Ketanserin
Ketanserin, a new selective 5-HT2-serotonergic antagonist, was used to: confirm its hypotensive efficacy in acute and long-term treatment, determine its influence on the influence on the metabolism of serotonin (5-HT) and catecholamines, and elucidate their mutual relationship. Ketanserin was given intravenously to 10 patients with hypertensive crisis or resistant hypertension and orally to 15 patients with mild to severe hypertension for 1 year. Blood pressure, heart rate, 24-h urinary excretion of vanilmandelic acid (VMA; the major endproduct of catecholamines) and of 5-hydroxyindoleacetic acid (HIAA; the endproduct of serotonin metabolism), and platelet aggregation were measured. In doses normalizing blood pressure and platelet aggregation, ketanserin administered to hypertensive patients either intravenously in acute treatment or orally in chronic treatment caused: (a) decreased HIAA excretion (more marked in chronic than in acute treatment) and (b) simultaneous decrease in VMA excretion. It is concluded that the decisive sites of ketanserin action are the 5-HT2 receptors of platelets. The compound reduces platelet aggregation and the release of 5-HT, its metabolism, and, hence, the excretion of HIAA. The action of ketanserin on 5-HT2 receptors of vascular smooth muscle participates in the hypotensive effect of the drug but does not explain the decreased excretion of HIAA and VMA.