title: Endothelin-1 myocardial clearance, production, and effect on capillary permeability in vivo.
abstract: Myocardial metabolism of endothelin-1 (ET-1) and its effect on coronary microcirculatory exchanges were obtained in anesthetized dogs by combining the indicator-dilution technique with immunoreactive ET-1 measurements. The myocardium extracted 17.7 +/- 4.6% of tracer ET-1 (n = 12). Simultaneously measured ET-1 levels in the aorta (0.97 +/- 0.46 pg/ml) and coronary sinus (0.96 +/- 0.53 pg/ml) were not different, supporting a production of ET-1 by the heart that balances the amount extracted. Intracoronary infusion of ET-1 (5 ng.kg-1.min-1) increased coronary sinus ET-1 levels approximately 50-fold, decreased coronary blood flow per unit of interstitial space by approximately 30% (P = 0.006), and increased myocardial microcirculatory transit times (n = 6). Permeability to albumin was unaffected by ET-1, whereas the permeability-surface area product for sucrose decreased following derecruitment of myocardial capillaries. We conclude that there is a normal myocardial metabolic balance of ET-1 and that the heart marginally contributes to circulating ET-1. Pharmacological doses of ET-1 may adversely affect myocardial metabolism by reducing blood flow and the permeability-surface area product for small circulating substances.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Dupuis
authors.forename: C A
authors.initials: CA
authors.lastname: Goresky
authors.forename: C P
authors.initials: CP
authors.lastname: Rose
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: P
authors.initials: P
authors.lastname: Cernacek
authors.forename: A J
authors.initials: AJ
authors.lastname: Schwab
authors.forename: A
authors.initials: A
authors.lastname: Simard
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D019332:Endothelin-1 / Q000096:biosynthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D013599:Systole / Q000187:drug effects; D013997:Time Factors
chemical_list: D019332:Endothelin-1