Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans
Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans
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DOI：
10.1161/01.cir.0000141294.25130.54
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发表时间：
2004-09-14
期刊：
影响因子：
37.8
通讯作者：
Camici, PG
中科院分区：
文献类型：
--
作者：
Kaufmann, PA;Rimoldi, O;Camici, PG
背景一氧化氮（NO）是一种调节血管平滑肌张力的内皮介质，但它也可以通过调节血管张力的自主控制来发挥其心血管作用。我们评估了同时抑制内皮型（eNOS）和神经型（nNOS）NO合酶亚型对志愿者和（去神经）移植受体的心肌血流量（MBF）和冠状动脉血流储备（CFR）的影响。方法和结果-MBF（mL.min（-1）.g（-1））在休息时和腺苷诱导的充血期间用正电子发射断层扫描和O-15标记水进行测量。CFR计算为腺苷/静息MBF。在以下静脉输注期间重复测量：组1（n=12），盐水;组2（n=9），3 mg/kg N-G-单甲基-L-精氨酸（L-NMMA），其穿过血脑屏障并抑制eNOS和nNOS;组3（n=13），10 mg/kg L-NMMA;组4（n=8），滴定苯丙氨酸以模拟组3中的血流动力学变化;第5组（n=6），L-NMMA 10 mg/kg静脉滴注。干预后，第1、2和4组的充血MBF和CFR无变化。相比之下，充血MBF（+53%，P
Background-Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients.Methods and Results-MBF (mL.min(-1).g(-1)) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and O-15-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg N-G-monomethyl-L-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n=13), 10 mg/kg L-NMMA; group 4 (n=8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P