DIFFERENCES IN VASCULAR EFFECTS AND REMOVAL OF ENDOTHELIN-1 IN HUMAN LUNG, BRAIN, AND SKELETAL-MUSCLE

To investigate the effects and elimination of endothelin-1 in humans, an intravenous infusion of endothelin-1 (ET-1) (4 pmol kg-1 min-1 for 20 min) was given to 10 healthy volunteers. Arterial plasma endothelin -1 like immunoreactivity (ET-1-LI) increased eleven-fold. The fraction al extraction of ET-1-LI was 41% and 30% across the pulmonary and skel etal muscle vascular beds, respectively. The lung eliminated almost ha lf of the administered ET-1. No fractional extraction was found in the cerebral circulation. The pulmonary oxygen uptake (VO2) Was increased slightly by endothelin-1. Across both the cerebral and skeletal muscl e vascular beds the arterio-venous oxygen difference decreased (P < 0. 05), suggesting vasodilation, the effect lasting up to 1 h after the e nd of endothelin-1 infusion in the cerebral circulation. Arterial-pulm onary artery oxygen difference increased by 20%. ET-1 infusion led to a decrease in heart rate (10%), cardiac output (14%) and stroke volume (8%) (all with P < 0.05) as well as a 7% increase in mean arterial bl ood pressure. Pulmonary and systemic vascular resistance increased by 67% and 25%, respectively (P < 0.05). These results demonstrate the re gional differences in the removal of circulating endothelin-1, the lun g being mainly responsible for the plasma elimination. Endothelin-1 se ems to exert both vasoconstrictive and vasodilatory actions in humans, probably depending on differences in receptor populations and endothe lium configuration in various vascular beds.