Parent R, Hamdad N, Ming Z, Lavallée M
Department of Physiology, Université de Montréal, Que., Canada.
Cardiovasc Res. 1996 Apr;31(4):555-67.
To determine the differential effects of blockade of nitric oxide (NO) formation by an arginine analogue on basal and stimulated NO release in conductance and resistance coronary vessels.
In conscious dogs, instrumented for measuring coronary blood flow (CBF) and external epicardial coronary artery diameter (CD), intracoronary (ic) acetylcholine (ACH, 3.0 ng/kg), adenosine (ADENO 100.0 ng/kg) and nitroglycerin (NTG, 10.0 ng/kg) were injected before and after ic N omega-nitro-L-arginine methyl ester (L-NAME, 50.0 micrograms.kg-1 min-1 for 12 min) to block NO synthesis.
Before L-NAME, ACH increased CBF by 65.3 +/- 9.0 from 42.4 +/- 2.9 ml/min and CD by 0.199 +/- 0.035 from 3.374 +/- 0.193 mm. L-NAME failed to alter baseline CBF but reduced (P < 0.01) CD to 3.220 +/- 0.199 mm. CBF responses to ACH were smaller (P < 0.01) (32.8 +/- 5.3 ml/min) after L-NAME. In contrast, ACH-induced increases in CD (0.184 +/- 0.053 mm) were not altered. L-NAME did not change CBF responses to NTG but increased CD responses (0.345 +/- 0.062 vs 0.217 +/- 0.043 mm, P < 0.01). ADENO-induced increases in CBF were smaller after L-NAME (46.5 +/- 5.6 vs 79.8 +/- 10.9 ml/min, P < 0.01). Increases in CD created by ADENO, a flow-dependent phenomenon, were nearly abolished after L-NAME (0.043 +/- 0.018 vs 0.195 +/- 0.026 mm, P < 0.01) and partially restored by ic L-arginine. The effects of L-NAME on CBF and CD responses to ACH and ADENO continuously delivered into the coronary artery were similar to those of boluses.
L-NAME selectively reduced ACH-induced dilation in resistance coronary vessels but failed to prevent responses of conductance coronary vessels in spite of reducing baseline CD and blocking flow-dependent effects of ADENO. Therefore, blockade of NO formation resulted in disparate effects on receptor-operated dilation of resistance and conductance coronary vessels.
确定精氨酸类似物阻断一氧化氮（NO）生成对传导性和阻力性冠状动脉基础和刺激状态下NO释放的不同影响。
在清醒犬身上，通过仪器测量冠状动脉血流量（CBF）和心外膜冠状动脉外径（CD），在冠状动脉内（ic）注射Nω-硝基-L-精氨酸甲酯（L-NAME，50.0微克·千克-1·分钟-1，持续12分钟）以阻断NO合成前后，分别注射冠状动脉内（ic）乙酰胆碱（ACH，3.0纳克/千克）、腺苷（ADENO，100.0纳克/千克）和硝酸甘油（NTG，10.0纳克/千克）。
在注射L-NAME之前，ACH使CBF从42.4±2.9毫升/分钟增加了65.3±9.0，使CD从3.374±0.193毫米增加了0.199±0.035。L-NAME未能改变基础CBF，但使CD降低（P<0.01）至3.220±0.199毫米。注射L-NAME后，对ACH的CBF反应变小（P<0.01）（32.8±5.3毫升/分钟）。相比之下，ACH诱导的CD增加（0.184±0.053毫米）未改变。L-NAME未改变对NTG的CBF反应，但增加了CD反应（0.345±0.062对0.217±0.043毫米，P<0.01）。注射L-NAME后，ADENO诱导的CBF增加变小（46.5±5.6对79.8±10.9毫升/分钟，P<0.01）。由ADENO引起的、作为流量依赖性现象的CD增加在注射L-NAME后几乎完全消失（0.043±0.018对0.195±0.026毫米，P<0.01），并通过冠状动脉内注射L-精氨酸部分恢复。L-NAME对持续注入冠状动脉的ACH和ADENO的CBF和CD反应的影响与推注相似。
L-NAME选择性地降低了ACH诱导的阻力性冠状动脉扩张，但尽管降低了基础CD并阻断了ADENO的流量依赖性效应，仍未能阻止传导性冠状动脉的反应。因此，阻断NO生成对阻力性和传导性冠状动脉的受体介导性扩张产生了不同的影响。
