POTENT VASOCONSTRICTOR EFFECTS AND CLEARANCE OF ENDOTHELIN IN THE HUMAN FOREARM

The vascular effects of endothelin-1 in humans were investigated by infusion into the brachial artery of healthy volunteers. Endothelin-1 (5-500 pmol min-1) evoked potent and long lasting increase in forearm vascular resistance (FVR) and reduction in venous compliance, suggesting constriction of both resistance and capacitance vessels. The threshold for effect on forearm vascular resistance was at a calculated plasma concentration of 614 pmol 1(-1). Endothelin-1 was on a molar basis 10-20 times more potent than noradrenaline as constrictor of both resistance and capacitance vessels. The increase in forearm vascular resistance induced by endothelin-1 lasted more than 30 min and that by noradrenaline less than 3 minutes. The endothelin-1-like immunoreactivity collected in the venous effluent during the infusion was 10-26% of the calculated arterial plasma concentration, indicating local removal of endothelin. After the infusion of endothelin-1 the urine concentration of prostacyclin metabolite increased significantly, indicating release of prostacyclin, whereas the concentration of thromboxane metabolite did not increase. It is concluded that endothelin-1 is a highly potent constrictor of human resistance and capacitance vessels, that it causes release of prostacyclin and that circulating endothelin-1 is efficiently removed by the forearm in vivo.