Effect of Ketanserin on Phenylephrine-Dependent Changes in Splanchnic Hemodynamics and Systemic Blood Pressure in Healthy Subjects

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Abstract
The effect of ketanserin on basal status and phenylephrine-dependent changes in arterial blood pressure and splanchnic hemodynamics was studied in 7 healthy subjects. The drug was administered as an i.v. bolus of 10 mg followed by infusion of 4 mg/h. After a basal period of saline or ketanserin infusion, phenylephrine was infused at a constant rate in a fixed dose sequence of 1, 2 and 3 .mu.g/kg min. Blood pressure was measured intraarterially. Splanchnic blood flow, mean wedged hepatic blood pressure and splanchnic vascular resistance were assessed using hepatic venous catheter technique using indocyanine green dye. At steady-state plasma concentrations, basal arterial pressure and heart rate were not altered in this small group of normal subjects; mean wedged hepatic venous pressure was lowered by ketanserin. During saline infusion, phenylephrine provoked a dose-dependent rise in arterial and wedged hepatic blood pressure: these effects were attenuated by ketanserin. Phenylephrine induced a significant but not dose-dependent decrease in estimated splanchnic blood flow. Ketanserin did not relevantly influence basal or phenylephrine-dependent splanchnic blood flow. Evidently, the hypotensive action of ketanserin is in part related to an interaction at .alpha.1-adrenoceptors. A dissociation of effects on vascular .alpha.-receptors seems to exist in the splanchnic and systemic circulations.