Canty J M, Schwartz J S
Department of Medicine, State University of New York at Buffalo, School of Medicine and Biomedical Sciences 14215-3012.
Circulation. 1994 Jan;89(1):375-84. doi: 10.1161/01.cir.89.1.375.
Although epicardial coronary arteries dilate in response to changes in flow, the mechanisms responsible for this and the mechanical stimuli that are sensed by the endothelium are not completely defined. We performed the present study to determine the importance of nitric oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs.
Dogs were chronically instrumented with a circumflex coronary occluder, piezoelectric crystals to measure epicardial diameter, and a coronary artery catheter placed distal to the crystals for 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 IV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 micrograms/min) from 140 +/- 23 (+/- SEM) to 46 +/- 20 microns (P < .05). Epicardial dilation to sustained increases in mean coronary artery at a constant heart rate. Intracoronary adenosine increased mean flow to the same extent (180 +/- 21 versus 177 +/- 24 mL/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 microns under control conditions and 294 +/- 67 microns 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 increased to a similar level (78 +/- 9 versus 75 +/- 9 mL/min after L-NAME), but the epicardial diameter change to pacing was attenuated from 170 +/- 29 microns under control conditions to 54 +/- 23 microns after L-NAME (P < .01).
These results demonstrate that in vivo, nitric oxide production is primarily responsible for eliciting epicardial coronary vasodilation to endothelium-dependent agonists and changes in coronary flow pulse frequency. The failure of L-NAME to affect epicardial vasodilation during sustained increases in mean flow when pulse frequency is held constant suggests that additional mechanisms are involved in flow-mediated vasodilation of epicardial coronary arteries.
尽管心外膜冠状动脉会随着血流变化而扩张，但其背后的机制以及内皮细胞所感知的机械刺激尚未完全明确。我们开展本研究以确定一氧化氮在引起清醒犬冠状动脉循环中的心外膜扩张以应对平均血流和脉搏频率持续变化方面的重要性。
犬长期植入回旋支冠状动脉封堵器、用于测量心外膜直径的压电晶体以及置于晶体远端用于冠状动脉内药物输注的冠状动脉导管。研究在清醒状态的犬身上进行。我们通过静脉注射精氨酸类似物Nω-硝基-L-精氨酸甲酯（L-NAME，10mg/kg）抑制一氧化氮生成，这使心外膜动脉直径对左心房输注乙酰胆碱（10μg/min）的变化从140±23（±SEM）微米减弱至46±20微米（P<.05）。在恒定心率下，心外膜对冠状动脉平均血流持续增加的扩张。冠状动脉内腺苷使平均血流增加到相同程度（L-NAME后为180±21对177±24mL/min，P=无显著性差异），但抑制一氧化氮生成对血流介导的心外膜扩张无影响，在对照条件下冠状动脉直径增加264±36微米，L-NAME后增加294±67微米（P=无显著性差异）。相反，当通过起搏将脉搏频率增加到每分钟200次时，平均冠状动脉血流增加到相似水平（L-NAME后为78±9对75±9mL/min），但起搏引起的心外膜直径变化从对照条件下的170±29微米减弱至L-NAME后的54±23微米（P<.01）。
这些结果表明，在体内，一氧化氮生成主要负责引起心外膜冠状动脉对内皮依赖性激动剂和冠状动脉血流脉搏频率变化的血管舒张。当脉搏频率保持恒定时，L-NAME在平均血流持续增加期间未能影响心外膜血管舒张，这表明心外膜冠状动脉血流介导的血管舒张涉及其他机制。
