NITRIC-OXIDE MEDIATES FLOW-DEPENDENT EPICARDIAL CORONARY VASODILATIONTO CHANGES IN PULSE FREQUENCY BUT NOT MEAN FLOW IN CONSCIOUS DOGS

Background Although epicardial coronary arteries dilate in response to changes in how, the mechanisms responsible for this and the mechanica l stimuli that are sensed by the endothelium are not completely define d. We performed the present study to determine the importance of nitri c oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs . Method and Results Dogs were chronically instrumented with a circumf lex coronary occluder, piezoelectric crystals to measure epicardial di ameter, and a coronary artery catheter placed distal to the crystals f or intracoronary drug infusion. Studies were conducted in dogs in the conscious state. We inhibited nitric oxide production by administering the arginine analog N-omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg TV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 mu g/min) from 140+/-23 (/-SEM) to 46+/-20 mu m (P<.05). Epicardial dilation to sustained incre ases in mean coronary flow was examined by infusing adenosine into the distal coronary artery at a constant heart rate. Intracoronary adenos ine increased mean flow to the same extent (180+/-21 versus 177+/-24 m L/min after L-NAME, P=NS), but inhibiting nitric oxide production had no effect on flow-mediated epicardial dilation, with coronary diameter increasing by 264+/-36 mu m under control conditions and 294+/-67 mu m after L-NAME (P=NS). In contrast, when pulse frequency was increased by pacing to a rate of 200 beats per minute, mean coronary flow incre ased to a similar level (78+/-9 versus 75+/-9 mL/min after L-NAME), bu t the epicardial diameter change to pacing was attenuated from 170+/-2 9 mu m under control conditions to 54+/-23 mu m after L-NAME (P<.01). Conclusions These results demonstrate that in vivo, nitric oxide produ ction is primarily responsible for eliciting epicardial coronary vasod ilation to endothelium-dependent agonists and changes in coronary how pulse frequency. The failure of L-NAME to affect epicardial vasodilati on during sustained increases in mean flow when pulse frequency is hel d constant suggests that additional mechanisms are involved in flow-me diated vasodilation of epicardial coronary arteries.