β 2 -Adrenergic Dilation of Resistance Coronary Vessels Involves K ATP Channels and Nitric Oxide in Conscious Dogs

Abstract

Background We considered that β 2 -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 β 1 -adrenergic blockade, intracoronary (IC) injections of acetylcholine (ACh), nitroglycerin (NTG), and pirbuterol (PIR), a selective β 2 -adrenergic agonist, were performed before and after blockade of NO formation with IC N ω -nitro- l -arginine methyl ester (L-NAME, 50 μg·kg −1 ·min −1 ×12 minutes) or blockade of K ATP channels with IC glibenclamide (25 μg·kg −1 ·min −1 ×12 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 β 2 -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.