title: Exercise limits the production of endothelin in the coronary vasculature.
abstract: We previously demonstrated that endothelin (ET)-mediated coronary vasoconstriction wanes with increasing exercise intensity via a nitric oxide- and prostacyclin-dependent mechanism (Ref. 23). Therefore, we hypothesized that the waning of ET coronary vasoconstriction during exercise is the result of decreased production of ET and/or decreased ET receptor sensitivity. We investigated coronary ET receptor sensitivity using intravenous infusion of ET and coronary ET production using intravenous infusion of the ET precursor Big ET, at rest and during continuous treadmill exercise at 3 km/h in 16 chronically instrumented swine. In the systemic vasculature, Big ET and ET induced similar changes in hemodynamic parameters at rest and during continuous exercise at 3 km/h, indicating that exercise does not alter ET production or receptor sensitivity in the systemic vasculature. In the coronary vasculature, infusion of ET resulted in similar dose-dependent decreases in coronary blood flow and coronary venous oxygen tension and saturation at rest and during exercise. In contrast, administration of Big ET resulted in dose-dependent decreases in coronary blood flow, as well as coronary venous oxygen tension and saturation at rest. These effects of Big ET were significantly reduced during exercise. Altogether, our data indicate that continuous exercise at 3 km/h attenuates ET-mediated coronary vasoconstriction through reduced production of ET from Big ET rather than through reduced ET sensitivity of the coronary vasculature. The decreased ET production during exercise likely contributes to metabolic coronary vasodilation.
authors.affiliation: Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, he Netherlands. d.merkus@erasmusmc.nl
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: de Beer
authors.forename: Shawn B
authors.initials: SB
authors.lastname: Bender
authors.forename: Yannick J
authors.initials: YJ
authors.lastname: Taverne
authors.forename: Fen
authors.initials: F
authors.lastname: Gao
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D023421:Models, Animal; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017466:Receptors, Endothelin / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D016232:Endothelins; D017466:Receptors, Endothelin