Endothelin-dependent tone limits acetylcholine-induced dilation of resistance coronary vessels after blockade of NO formation in conscious dogs.
Nitric oxide (NO) impairs endothelin (ET) formation and/or action in isolated vessels. We hypothesized that ET may magnify the consequences of NO formation blockade on receptor-operated dilation of resistance coronary vessels in conscious dogs. In conscious instrumented dogs, graded intracoronary (IC) doses of acetylcholine (ACh) were delivered before IC administration of Nomega-nitro-L-arginine methyl ester (L-NAME), after L-NAME, and after L-NAME plus IC bosentan, an ETA/ETB receptor blocker. Before L-NAME, ACh (100 ng. kg-1. min-1) increased coronary blood flow (CBF) by 43+/-4% from 47+/-6 mL. min-1. After L-NAME, ACh failed to increase CBF (-3+/-2% from 50+/-7 mL. min-1). CBF responses to ACh were partially restored (+10+/-2% from 50+/-7 mL. min-1, P<0.01) after the addition of bosentan. Bosentan alone (without L-NAME) did not alter CBF responses to ACh. Blockade of ETA (Ro 61-1790) but not ETB (Ro 46-8443) receptors partially restored CBF responses to ACh after L-NAME. Myocardial immunoreactive ET levels in the perfusion territories of the circumflex and left anterior descending coronary arteries did not differ. ETA-dependent tone magnified the inhibitory effects of blockade of NO formation on receptor-operated dilation to ACh in resistance coronary vessels. Presumably, stimulated NO release has an inhibitory action on endogenous ET production and/or action at the level of resistance coronary vessels.
Ming
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Z
Department of Physiology and Surgery, Faculty of Medicine, Université de Montréal, and Institut de Cardiologie de Montréal, Montréal, Québec, Canada.
Parent
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Thorin
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Lavallée
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester