Contribution of endogenous endothelin to large epicardial coronary artery tone in dogs and humans.
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.
Thorin
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Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal H3C 3J7, Montréal, Québec, Canada H1T 1C8.
Parent
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Ming
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Lavallée
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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
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