Paulus W J, Kästner S, Vanderheyden M, Shah A M, Drexler H
Cardiovascular Center, O.L.V. Ziekenhuis, Aalst, Belgium.
J Am Coll Cardiol. 1997 May;29(6):1332-8. doi: 10.1016/s0735-1097(97)00056-9.
In the present study, we investigated, in transplant recipients, whether L-arginine (L-arg) potentiates the myocardial contractile effects of receptor-mediated coronary endothelial stimulation. Moreover, because inducible nitric oxide synthase (iNOS) is frequently expressed in transplanted myocardium, we also performed intracoronary infusion of L-arg in the absence of receptor-mediated coronary endothelial stimulation to investigate whether similar left ventricular (LV) contractile effects could be induced by providing more substrate for iNOS.
Nitric oxide (NO), released from coronary endothelium after receptor-mediated stimulation by substance P (SP), affects vascular smooth muscle tone and modulates LV contractile performance. L-arg augments receptor-mediated endothelium-dependent coronary vasodilation in transplant recipients by increasing substrate availability for endothelial NO production.
Sixteen transplant recipients were studied at the time of annual coronary angiography. In eight transplant recipients, microtip LV pressures were recorded before and during intracoronary (IC) SP (20 pmol/min) and after the addition of IC L-arg (160 mumol/min) to IC SP. In eight transplant recipients, microtip LV pressures were recorded before and during IC L-arg (160 mumol/min) alone, and in six of these patients, endomyocardial biopsy samples were obtained to detect the expression of iNOS gene by reverse transcription-polymerase chain reaction.
Addition of IC L-arg to IC SP induced a fall (mean +/- SEM) in LV peak systolic pressure (-16 +/- 4 mm Hg), which was larger (p < 0.01) than that observed during IC SP (-7 +/- 2 mm Hg). During IC L-arg alone, there was no change in LV peak systolic pressure despite the presence of iNOS mRNA in five of the six biopsy samples.
In transplant recipients, L-arg potentiates the paracrine myocardial contractile effects of receptor-mediated coronary endothelial stimulation, probably by providing more substrate for endothelial NO production. Despite the myocardial expression of iNOS gene, L-arg alone fails to elicit similar contractile effects.
在本研究中，我们调查了移植受者中L-精氨酸（L-arg）是否能增强受体介导的冠状动脉内皮刺激对心肌收缩的影响。此外，由于诱导型一氧化氮合酶（iNOS）在移植心肌中经常表达，我们还在没有受体介导的冠状动脉内皮刺激的情况下进行了冠状动脉内注入L-arg，以研究通过为iNOS提供更多底物是否能诱导类似的左心室（LV）收缩效应。
在P物质（SP）受体介导的刺激后，冠状动脉内皮释放的一氧化氮（NO）会影响血管平滑肌张力并调节LV收缩性能。L-arg通过增加内皮NO生成的底物可用性，增强了移植受者中受体介导的内皮依赖性冠状动脉舒张。
在年度冠状动脉造影时对16名移植受者进行研究。在8名移植受者中，记录冠状动脉内（IC）注入SP（20 pmol/分钟）之前和期间以及在IC SP中加入IC L-arg（160 μmol/分钟）之后的微尖端LV压力。在8名移植受者中，记录单独IC L-arg（160 μmol/分钟）之前和期间的微尖端LV压力，并且在其中6名患者中，获取心内膜活检样本，通过逆转录-聚合酶链反应检测iNOS基因的表达。
在IC SP中加入IC L-arg导致LV收缩压峰值下降（平均值±标准误）（-16±4 mmHg），这比IC SP期间观察到的下降幅度更大（p<0.01）（-7±2 mmHg）。在单独IC L-arg期间，尽管6个活检样本中有5个存在iNOS mRNA，但LV收缩压峰值没有变化。
在移植受者中，L-arg可能通过为内皮NO生成提供更多底物，增强了受体介导的冠状动脉内皮刺激的旁分泌心肌收缩效应。尽管心肌中存在iNOS基因表达，但单独使用L-arg未能引发类似的收缩效应。
