BETA(2)-ADRENERGIC DILATION OF RESISTANCE CORONARY VESSELS INVOLVES K-ATP CHANNELS AND NITRIC-OXIDE IN CONSCIOUS DOGS

Background We considered that beta(2)-adrenergic stimulation may dilat e resistance coronary vessels by opening ATP-sensitive potassium (K-AT P) channels, thereby triggering NO formation. Methods and Results In c onscious instrumented dogs after beta(1)-adrenergic blockade, intracor onary (IC) injections of acetylcholine (ACh), nitroglycerin (NTG), and pirbuterol (PIR), a selective beta(2)-adrenergic agonist, were perfor med before and after blockade of NO formation with IC N-omega-nitro-L- arginine methyl ester (L-NAME, 50 mu g . kg(-1). min(-1) x 12 minutes) or blockade of K-ATP channels with IC glibenclamide (25 mu g . kg(-1) . min(-1) x 12 minutes followed by 2 mu g . 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-NA ME. Increases in CBF to ACh were also reduced by L-NAME, but NTG respo nses were not. Before glibenclamide, PIR increased CBF by 33 +/- 5 fro m 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 glibenc lamide. Lemakalim, a selective opener of K-ATP channels, caused dose-d ependent increases in CBF that were partially inhibited by L-NAME. In experiments in which CBF was controlled, the fall in distal coronary p ressure caused by PIR was less after L-NAME or glibenclamide than befo re. Conclusions beta(2)-Adrenergic dilation of resistance coronary ves sels involves both the opening of K-ATP channels and NO formation. L-N AME antagonized lemakalim responses consistent with a link between the opening of K-ATP channels and NO formation in canine resistance coron ary vessels.