Shen W, Hintze T H, Wolin M S
Department of Physiology, New York Medical College, Valhalla 10595, USA.
Circulation. 1995 Dec 15;92(12):3505-12. doi: 10.1161/01.cir.92.12.3505.
Nitric oxide (NO) is known to be an inhibitor of mitochondrial function. However, the physiological significance of endothelium-derived NO in the control of tissue respiration is not established.
Tissue O2 consumption by skeletal muscle slices of the triceps brachii of normal dogs was measured with a Clark-type O2 electrode/tissue bath system at 37 degrees C. S-Nitroso-N-acetylpenicillamine (SNAP), carbachol (CCh), or bradykinin (BK) decreased tissue O2 consumption by 12 +/- 3% to 55 +/- 8%, 15 +/- 6% to 36 +/- 11%, or 21 +/- 5% to 42 +/- 4% at doses of 10(-7) to 10(-4) mol/L, respectively. The effects of both CCh and BK but not SNAP were eliminated by nitro-L-arginine (NLA, 10(-4) mol/L), consistent with SNAP decomposing to release NO and both CCh and BK stimulating endogenous NO production from L-arginine. Oxygen consumption was also decreased by 8-bromo-cGMP. The mitochondrial uncoupler dinitrophenol blocked the effects of 8-bromo-cGMP but only slightly altered those of SNAP, indicating that the major site of action of NO is the mitochondria. In normal, chronically instrumented, resting conscious dogs, blockade of NO synthase by NLA increased mean arterial pressure by 28 +/- 2.5 mm Hg and hind limb vascular resistance by 114 +/- 12% and decreased blood flow by 39 +/- 3%. Most important, NLA also increased O2 uptake by 55 +/- 9% in hind limb skeletal muscle (P < .05), associated with decreases in PO2 and O2 saturation and an increase in reduced hemoglobin in hind limb venous blood.
Our results indicate that NO release from vascular endothelial cells appears to play an important physiological role in the regulation of tissue mitochondrial respiration in skeletal muscle and perhaps other organ systems.
一氧化氮（NO）是已知的线粒体功能抑制剂。然而，内皮源性NO在组织呼吸控制中的生理意义尚未明确。
用Clark型氧电极/组织浴系统在37℃下测量正常犬肱三头肌骨骼肌切片的组织氧消耗。在10⁻⁷至10⁻⁴mol/L剂量下，S-亚硝基-N-乙酰青霉胺（SNAP）、卡巴胆碱（CCh）或缓激肽（BK）分别使组织氧消耗降低12±3%至55±8%、15±6%至36±11%或21±5%至42±4%。硝基-L-精氨酸（NLA，10⁻⁴mol/L）消除了CCh和BK的作用，但未消除SNAP的作用，这与SNAP分解释放NO以及CCh和BK刺激L-精氨酸产生内源性NO一致。8-溴-cGMP也降低了氧消耗。线粒体解偶联剂二硝基苯酚阻断了8-溴-cGMP的作用，但仅轻微改变了SNAP的作用，表明NO的主要作用位点是线粒体。在正常、长期植入仪器、静息清醒的犬中，NLA阻断一氧化氮合酶使平均动脉压升高28±2.5mmHg，后肢血管阻力升高114±12%，血流量降低39±3%。最重要的是，NLA还使后肢骨骼肌的氧摄取增加55±9%（P<0.05），同时后肢静脉血中的PO₂和氧饱和度降低，还原血红蛋白增加。
我们的结果表明，血管内皮细胞释放的NO似乎在骨骼肌以及可能其他器官系统的组织线粒体呼吸调节中发挥重要的生理作用。
