Massive regional differences in the vascular effects of endothelin

Endothelin was infused into seven anaesthetized open-chest rabbits during three 10-min periods, so that cumulative doses of 0.01, 0.1 and 1 nmol/kg were achieved. Endothelin increased blood pressure and caused systemic vasoconstriction only at the highest dose, but decreased the myocardial contractile force (measured with a strain-gauge) at all doses. In contrast to the modest systemic haemodynamic changes, vascular effects (measured with tracer microspheres) were found at each dose level and varied greatly from vasodilator (hepatic artery), through biphasic (spleen) to pure vasoconstrictor (adrenals, pancreas, stomach, colon) effects. Systemic circulatory parameters poorly reflect the regional vascular activity of endothelin.