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(Circulation. 1997;95:1568-1576.)
© 1997 American Heart Association, Inc.

Articles

ß₂-Adrenergic Dilation of Resistance Coronary Vessels Involves K_ATP Channels and Nitric Oxide in Conscious Dogs

Zhi Ming, MD, PhD; Robert Parent, PhD; Michel Lavallée, PhD

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

Correspondence to Michel Lavallée, Institut de Cardiologie de Montréal, 5000, Bélanger St E, Montréal, Québec, Canada H1T 1C8.

Background We considered that ß₂-adrenergic stimulation may dilate resistance coronary vessels by opening ATP-sensitive potassium (K_ATP) channels, thereby triggering NO formation.

Methods and Results In conscious instrumented dogs after ß₁-adrenergic blockade, intracoronary (IC) injections of acetylcholine (ACh), nitroglycerin (NTG), and pirbuterol (PIR), a selective ß₂-adrenergic agonist, were performed before and after blockade of NO formation with IC N-nitro-L-arginine methyl ester (L-NAME, 50 µg·kg^-1·min^-1x12 minutes) or blockade of K_ATP channels with IC glibenclamide (25 µg·kg^-1·min^-1x12 minutes followed by 2 µg·kg^-1·min^-1). PIR (50.0 ng/kg) increased coronary blood flow (CBF) by 32±6 from 43±7 mL/min and by only 11±2 (P<.01) from 40±7 mL/min after L-NAME. Increases in CBF to ACh were also reduced by L-NAME, but NTG responses were not. Before glibenclamide, PIR increased CBF by 33±5 from 45±7 mL/min and by only 14±3 (P<.01) from 36±5 mL/min thereafter. CBF responses to ACh and NTG were maintained after glibenclamide. Lemakalim, a selective opener of K_ATP channels, caused dose-dependent increases in CBF that were partially inhibited by L-NAME. In experiments in which CBF was controlled, the fall in distal coronary pressure caused by PIR was less after L-NAME or glibenclamide than before.

Conclusions ß₂-Adrenergic dilation of resistance coronary vessels involves both the opening of K_ATP channels and NO formation. L-NAME antagonized lemakalim responses consistent with a link between the opening of K_ATP channels and NO formation in canine resistance coronary vessels.

Key Words: endothelium • endothelium-derived factors • microcirculation • receptors, adrenergic, beta

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