Effects of calcium channel blockade on the hemodynamic responses to endothelin infusion in conscious sheep.

The hemodynamic responses to bolus injection of endothelin I (ET) at 5, 15, and 50 micrograms were examined in conscious sheep (n = 5) before and after infusion of nisoldipine at 25 micrograms/kg/h. Endothelin produced dose-dependent increases in mean arterial pressure (MAP + 87 +/- 6 mm Hg at 50 micrograms) and calculated total peripheral resistance (CTPR + 54 +/- 15 mm Hg/L/min at 50 micrograms) and decreases in heart rate (HR - 34 +/- 6 beats/min at 50 micrograms) and cardiac output (CO - 2.6 +/- 0.3 L/min at 50 micrograms) but no change in stroke volume (SV). Nisoldipine attenuated (P less than .05) the endothelin-induced changes in MAP (+26 +/- 3 mm Hg at 5 micrograms) and CTPR (+13.0 +/- 2.1 mm Hg/L/min at 50 micrograms), but not the fall in heart rate or cardiac output. These data are compatible with the hypothesis that vasoconstrictor effects of ET in sheep are in part dependent on influx of calcium through L-type channels.