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(Hypertension. 1998;32:844-848.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Endothelin-Dependent Tone Limits Acetylcholine-Induced Dilation of Resistance Coronary Vessels After Blockade of NO Formation in Conscious Dogs

Zhi Ming; Robert Parent; Éric Thorin; ; Michel Lavallée

From the Department of Physiology and Surgery, Faculty of Medicine, Université de Montréal, and Institut de Cardiologie de Montréal, Montréal, Québec, Canada.

Correspondence to Michel Lavallée, Institut de Cardiologie de Montréal, 5000 East Bélanger St, Montréal, Québec, Canada, H1T 1C8. E-mail lavallem{at}icm.umontreal.ca

Abstract—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 N-nitro-L-arginine methyl ester (L-NAME), after L-NAME, and after L-NAME plus IC bosentan, an ET_A/ET_B 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 ET_A (Ro 61-1790) but not ET_B (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. ET_A-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.

Key Words: endothelium-derived factors • endothelin • acetylcholine • endothelium • microcirculation

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