Quyyumi A A, Dakak N, Andrews N P, Husain S, Arora S, Gilligan D M, Panza J A, Cannon R O
Cardiology Branch, National Heart, Lung, and Blood Institute/National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1995 Apr;95(4):1747-55. doi: 10.1172/JCI117852.
The bioavailability of nitric oxide (NO) in the human coronary circulation at rest and after acetylcholine (ACH)-induced vasodilation was investigated in 32 patients with angiographically normal coronary arteries. The effects of intracoronary L-NG monomethyl arginine (L-NMMA) were investigated at rest and after ACH, sodium nitroprusside, and adenosine. L-NMMA (64 mumol/min) increased resting coronary vascular resistance by 22% (P < 0.001), reduced distal epicardial coronary artery diameter by 12.6% (P < 0.001), and inhibited ACH-induced coronary epicardial and microvascular vasodilation. These effects were reversed with intracoronary L-arginine. L-NMMA did not inhibit dilation in response to sodium nitroprusside and adenosine. 23 patients were exposed to one or more coronary risk factors. The vasoconstrictor effect of L-NMMA on the epicardial and microvessels was greater in patients free of risk factors: Coronary vascular resistance was 36% higher in patients without risks, compared to 17% higher in patients with risks (P < 0.05). Both epicardial and microvascular dilator effects of ACH were greater in patients without risk factors, and the inhibition of these effects by L-NMMA was also greater in patients without risk factors. Thus: (a) NO contributes importantly to resting epicardial and coronary microvascular tone, (b) coronary vascular dilation in response to ACH is predominantly due to increased production of NO, and (c) despite the absence of angiographic evidence of atherosclerosis, exposure to coronary risk factors is associated with reduced resting and stimulated bioavailability of NO from the human coronary circulation.
在32例冠状动脉造影正常的患者中，研究了静息状态下及乙酰胆碱（ACH）诱导血管舒张后人体冠状动脉循环中一氧化氮（NO）的生物利用度。研究了冠状动脉内注射L-NG单甲基精氨酸（L-NMMA）在静息状态下以及ACH、硝普钠和腺苷作用后的效果。L-NMMA（64 μmol/min）使静息冠状动脉血管阻力增加22%（P<0.001），使心外膜冠状动脉远端直径减小12.6%（P<0.001），并抑制ACH诱导的冠状动脉心外膜和微血管舒张。冠状动脉内注射L-精氨酸可逆转这些作用。L-NMMA不抑制对硝普钠和腺苷的舒张反应。23例患者暴露于一种或多种冠状动脉危险因素。无危险因素患者中，L-NMMA对心外膜和微血管的血管收缩作用更强：无危险因素患者的冠状动脉血管阻力比有危险因素患者高36%，而有危险因素患者高17%（P<0.05）。ACH对心外膜和微血管的舒张作用在无危险因素患者中更强，L-NMMA对这些作用的抑制在无危险因素患者中也更强。因此：（a）NO对静息心外膜和冠状动脉微血管张力起重要作用；（b）ACH诱导的冠状动脉血管舒张主要是由于NO生成增加；（c）尽管没有动脉粥样硬化的血管造影证据，但暴露于冠状动脉危险因素与人体冠状动脉循环中静息和刺激状态下NO的生物利用度降低有关。
