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 fractional extraction of ET-1-LI was 41% and 30% across the pulmonary and skeletal muscle vascular beds, respectively. The lung eliminated almost half 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 muscle vascular beds the arterio-venous oxygen difference decreased (P < 0.05), suggesting vasodilation, the effect lasting up to 1 h after the end of endothelin-1 infusion in the cerebral circulation. Arterial-pulmonary 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 blood pressure. Pulmonary and systemic vascular resistance increased by 67% and 25%, respectively (P < 0.05). These results demonstrate the regional differences in the removal of circulating endothelin-1, the lung being mainly responsible for the plasma elimination. Endothelin-1 seems to exert both vasoconstrictive and vasodilatory actions in humans, probably depending on differences in receptor populations and endothelium configuration in various vascular beds.
Weitzberg
E
E
Department of Anaesthesiology and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
Ahlborg
G
G
Lundberg
J M
JM
D000328:Adult; D001921:Brain / Q000378:metabolism*; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D011863:Radioimmunoassay; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D010100:Oxygen