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Nifedipine antagonizes alpha-adrenoceptor mediated splanchnic and systemic vasoconstriction in man
Abstract:
Aim of the study was to investigate whether nifedipine interacts with alpha1-mediated splanchnic and systemic vasoconstriction in man. The effects of nifedipine on basal and phenylephrine (PE)-induced hemodynamic changes were studied in 6 normotensive men, using the hepatic venous catheter technique (indocyanine-green) and the thermodilution method. After a baseline period, nifedipine was given by constant infusion (0.5 microgram/kg/min) and, after equilibration, PE was infused at a constant rate in a dose sequence of 1, 2, 3, and 4 micrograms/kg/min, until the systolic blood pressure was raised by 30 mmHg. Control trials without nifedipine (saline) were also performed in each subject. At basal conditions nifedipine decreased systemic blood pressure and total systemic vascular resistance (TSVR) as well as total pulmonary vascular resistance (TPVR), and increased cardiac output (CO). PE provoked a dose-dependent increase in systemic blood pressure, TSVR and TPVR, and decreased CO. These PE-effects were clearly attenuated by nifedipine. In the splanchnic vascular bed nifedipine increased estimated splanchnic blood flow (ESBF) and decreased splanchnic vascular resistance (SVR) at basal conditions. The PE-induced decrease in ESBF and increase in SVR were inhibited or attenuated (depending on PE-dosage) by nifedipine. We conclude that nifedipine counteracts alpha1-adrenoceptor mediated systemic and splanchnic vasoconstriction and therefore, might also be useful in the treatment of intestinal vasospasm.