NITRIC-OXIDE FORMATION CONTRIBUTES TO BETA-ADRENERGIC DILATION OF RESISTANCE CORONARY VESSELS IN CONSCIOUS DOGS

The contribution of the L-arginine/nitric oxide pathway to beta-adrene rgic dilation of resistance coronary vessels was examined in conscious dogs instrumented for measuring coronary blood How (CBF), left ventri cular (LV) wall thickening, and LV and aortic pressures and for intrac oronary injections of acetylcholine (0.003 mug/kg), nitroglycerin (0.1 75 mug/kg), and graded doses of isoproterenol (0.0005 to 0.004 mug/kg) . Peak increases in CBF with intracoronary isoproterenol (0.001 mug/kg ) averaged 105+/-10% from baseline. With acetylcholine, CBF increased by 158+/-11%, and with nitroglycerin, CBF increased by 139+/-10%. Afte r the administration of intracoronary N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mug/kg per minute for 12 minutes) to block nitric o xide synthesis from L-arginine, baseline CBF was not altered, and CBF increased by 49+/-7% with isoproterenol and by 94+/-6% with acetylchol ine; both values were smaller (P<.01) than those before the arginine a nalogue. With nitroglycerin, CBF was increased by 145+/-11%, not signi ficantly different from the value before L-NAME. Intracoronary L-argin ine (1.0 mg/kg per minute for 12 minutes), the precursor of nitric oxi de synthesis, partially reversed the inhibition of L-NAME on CBF respo nses to acetylcholine and isoproterenol. After beta1-adrenergic blocka de, CBF responses to isoproterenol and acetylcholine were also reduced (P<.05) by the arginine analogue. When increases in CBF were prevente d, peak changes in coronary vascular conductance with intracoronary bo lus doses of acetylcholine and isoproterenol were attenuated (P<.01) b y L-NAME. Thus, nitric oxide formation is an important intermediate in beta-adrenergic dilation of resistance coronary vessels in conscious dogs.