title: Contribution of endogenous endothelin to large epicardial coronary artery tone in dogs and humans.
abstract: Nitric oxide (NO) may normally impair endothelin (ET) activity in epicardial coronary arteries. Lifting this inhibitory feedback could reveal ET-dependent effects involving ET(A)- and/or ET(B)-receptor activation. In conscious dogs, the blockade of ET(A) receptors (intracoronary Ro-61-1790) increased external circumflex coronary artery diameter (CD) (sonomicrometry) by 0.10 +/- 0.01 from 3.04 +/- 0.12 mm (P < 0.01) without altering coronary blood flow (Doppler). Similarly, CD increased (0.09 +/- 0.01 from 2.91 +/- 0.14 mm; P < 0. 01) when Ro-61-1790 was given after blockade of NO formation with intracoronary N(omega)-nitro-L-arginine methyl ester (L-NAME). In contrast, ET(B)-receptor blockade (intracoronary Ro-46-8443) did not influence baseline CD with and without L-NAME. In vitro, increases in tension caused by N(omega)-nitro-L-arginine (L-NNA) or PGF(2alpha) in arterial rings were reduced by ET(A)- but not ET(B)-receptor blockade. ET(A)-receptor blockade also reduced the increase in tension caused by L-NNA in human coronary arterial rings. Thus ET(A) receptors, but not ET(B) receptors, account for ET-dependent constriction in canine epicardial coronary arteries in vivo. ET-dependent effects were independent of the level of NO formation in vitro and in vivo. In human epicardial coronary arterial rings, ET(A)-receptor blockade also caused significant relaxation.
authors.affiliation: Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal H3C 3J7, Montréal, Québec, Canada H1T 1C8.
authors.forename: E
authors.initials: E
authors.lastname: Thorin
authors.forename: R
authors.initials: R
authors.lastname: Parent
authors.forename: Z
authors.initials: Z
authors.lastname: Ming
authors.forename: M
authors.initials: M
authors.lastname: Lavallée
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010496:Pericardium / Q000502:physiology*; D011725:Pyridines; D011743:Pyrimidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000502:physiology*; D000096926:Benzenesulfonamides
chemical_list: D015237:Dinoprost; D004146:Dioxanes; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D019335:Nitroarginine; D011725:Pyridines; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D013777:Tetrazoles; C099180:Ro 46-8443; D000096926:Benzenesulfonamides; C109641:clazosentan