Cardiovascular effects of ketanserin in closed-chest anesthetized dogs

The cardiovascular effects of the selective 5 HT2-serotonergic antagonist Ketanserin (cumulative doses of 0.01, 0.04, 0.16, 0.64 and 2.5 mg.kg-1 i.v. at 30 min intervals) were investigated in closed-chest, anesthetized dogs with spontaneously beating hearts (n = 7) and in dogs with a fixed heart rate (n = 7). Besides, the effects of Ketanserin (0.04 mg.kg-1 i.v.) during serotonin infusion (median: 20 micrograms kg-1.min-1 i.v.) were studied (n = 7). Ketanserin, starting at 0.04 mg.kg-1, lowers arterial blood pressure through a decrease in systemic vascular resistance. The increase in heart rate after the injection of 0.16 mg.kg-1 and higher doses is likely reflexogenic in nature and secondary to the decrease in systemic vascular resistance. Ketanserin also induces a positive inotropic effect, starting at a dose of 0.16 mg.kg-1 as indicated by the increase in LV dP/dt max, LV dP/dt max/P and maximum aortic blood flow velocity at constant heart rate and in the presence of no change or a slight decrease in left ventricular end-diastolic pressure. Whether this is an intrinsic property of the compound remains subject to further investigation. Except for the increase in the variables related to left ventricular function, Ketanserin (0.04 mg.kg-1) blocks the serotonin induced circulatory and respiratory changes. The inhibition of serotonin induced pulmonary hypertension and bronchoconstriction was especially marked. The positive inotropic properties of serotonin were not blocked by Ketanserin, suggesting that this property of the amine is not 5 HT2-receptor mediated.