Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro. Implications for the development of heart failure.
Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro. Implications for the development of heart failure.
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DOI：
10.1161/01.res.79.3.381
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发表时间：
1996-09
影响因子：
20.1
通讯作者：
Yi-wu Xie;Weiqun Shen;Gong Zhao;Xiaobin Xu;M. Wolin;T. Hintze
中科院分区：
文献类型：
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作者：
Yi-wu Xie;Weiqun Shen;Gong Zhao;Xiaobin Xu;M. Wolin;T. Hintze
内源性一氧化氮（NO）调节心脏功能的机制尚不清楚。在这项研究中，通过Clark型O2电极在37 ℃下定量犬心脏左心室游离壁新鲜分离心肌段的O2消耗。S-亚硝基-N-乙酰青霉胺（SNAP，9 +/- 3%至50 +/- 8%）、缓激肽（BK，14 +/- 3%至30 +/- 5%）或卡巴胆碱（CCh，15 +/- 4%至29 +/- 4%）在剂量为10（-7）至10（-4）mol/L时显著降低组织耗氧量（平均值+/- SE，P <0.05）。10（-4）mol/L NG-硝基-L-精氨酸可阻断BK和CCh的作用，但不阻断SNAP的作用，这与BK和CCh分别刺激NO合成和SNAP分解释放NO的作用一致。相似剂量的8-Br-cGMP引起呼吸抑制，但程度较低（9 +/- 2%至14 +/- 6%）。线粒体解偶联剂，2，4-二硝基苯酚（在1 mmol/L），阻断8-Br-cGMP的影响，但不是SNAP，BK，或CCh的影响，这表明NO的主要作用部位是线粒体电子传递。起搏诱导心力衰竭犬心肌的基础耗氧率为251 +/- 21 nmol.min-1.g-1，比正常健康犬心脏心肌的耗氧率高54%。BK和CCh对O2消耗的抑制作用在衰竭的心脏组织中没有观察到，但SNAP显示出不变的抑制作用。因此，我们的研究结果表明，从微血管内皮释放的NO BK，刺激毒蕈碱受体，也许流速可能在心脏线粒体呼吸的控制中发挥重要的生理作用，这种调节功能的丧失可能有助于心力衰竭的发展。
The mechanism responsible for the regulation of cardiac function by endogenous nitric oxide (NO) remains unclear. In this investigation, O2 consumption by freshly isolated myocardial muscle segments from the left ventricular free wall of canine hearts was quantified by a Clark-type O2 electrode at 37 degrees C. S-nitroso-N-acetylpenicillamine (SNAP, 9 +/- 3% to 50 +/- 8%), bradykinin (BK, 14 +/- 3% to 30 +/- 5%), or carbachol (CCh, 15 +/- 4% to 29 +/- 4%) significantly attenuated tissue O2 consumption at doses of 10(-7) to 10(-4) mol/L (mean +/- SE, P < .05). The effects of BK and CCh, but not SNAP, were blocked by 10(-4) mol/L NG-nitro-L-arginine, consistent with both BK and CCh stimulating NO biosynthesis and with SNAP decomposing to release NO, respectively. Similar doses of 8-Br-cGMP caused a respiratory inhibition, but to a lesser extent (9 +/- 2% to 14 +/- 6%). A mitochondrial uncoupler, 2,4-dinitrophenol (at 1 mmol/L), blocked the effects of 8-Br-cGMP, but not those of SNAP, BK, or CCh, suggesting that the major site of action of NO is on mitochondrial electron transport. Myocardial muscle from dogs with pacing-induced heart failure had a basal O2 consumption rate of 251 +/- 21 nmol.min-1.g-1, which was 54% higher than the rate seen in muscle from normal healthy canine hearts. The inhibitory effects of BK and CCh on O2 consumption were not observed in failing cardiac tissue, but SNAP showed an unaltered inhibitory effect. Therefore, our results indicate that NO released from microvascular endothelium by BK, stimulation of muscarinic receptors, and perhaps flow velocity may play an important physiological role in the control of cardiac mitochondrial respiration, and the loss of this regulatory function may contribute to the development of heart failure.