(Circulation. 1996;94:2077-2082.)
© 1996 American Heart Association, Inc.
Articles |
Comparable Potent Coronary Constrictor Effects of Endothelin-1 and Big Endothelin-1 in Humans
the Department of Cardiology, Karolinska Hospital (J.P.), Department of Clinical Physiology, Huddinge Hospital (L.K., G.A.), and Department of Physiology and Pharmacology, Karolinska Institute (J.M.L), Stockholm, Sweden.
Correspondence to Dr J. Pernow, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Background Endothelin-1 (ET-1) is a potent vasoconstrictor produced from the precursor big ET-1 in endothelial cells. The coronary effects of these peptides in humans in vivo are unknown. Therefore, the effects of ET-1 and big ET-1 on coronary blood flow in relation to plasma ET-1 and big ET-1 levels were compared in healthy subjects.
Methods and Results The peptides were infused intravenously at the rates of 0.2, 1, and 8 pmol/kg per minute. Each dose was administered for 20 minutes except the highest dose of ET-1, which was administered for 10 minutes. ET-1 and big ET-1 evoked dose-related increases in mean arterial blood pressure from 93±4 to 107±4 mm Hg and from 89±2 to 122±5 mm Hg, respectively, at the highest dose. ET-1 and big ET-1 reduced coronary sinus blood flow, measured with thermodilution, by a maximum of 25±4% and 28±8% and increased coronary vascular resistance by 50±9% and 107±26%, respectively. Coronary sinus, but not arterial, oxygen saturation was reduced in parallel with the coronary sinus blood flow. The effects of ET-1 and big ET-1 were similar at corresponding time points. During infusion of ET-1, a 19±5% extraction of ET-1 was observed over the coronary vascular bed (P<.05). Administration of big ET-1 elevated arterial plasma ET-1 levels by 2.4-fold, and after correction for the local extraction of ET-1, a myocardial production of ET-1 was observed.
Conclusions ET-1 and big ET-1 induce comparable increases in blood pressure and coronary constriction in humans in vivo. The results also suggest a net local removal of circulating ET-1 and big ET-1 and a local conversion of big ET-1 into ET-1 within the coronary vascular bed.
Key Words: blood flow • endothelin • hemodynamics • oxygen • vasoconstriction
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