Williams Jeffrey G, Rincon-Skinner Tibisay, Sun Dong, Wang Zipping, Zhang Suhua, Zhang Xiaoping, Hintze Thomas H
New York Medical College, Valhalla, NY 10595, USA.
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2479-86. doi: 10.1152/ajpheart.00036.2006. Epub 2007 Jul 20.
We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MVo(2)) and oxygen delivery during pregnancy. Awake dogs were studied using echocardiography before and at 40 days, 50 days, and 60 days (60D) of pregnancy and at approximately 14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MVO(2) of left ventricular tissue samples was measured in vitro in response to increasing doses of bradykinin, enalapril maleate, and amlodipine. We examined the changes in passive diameter and flow-dependant arteriolar dilation of coronary arterioles. Echocardiography indicated increases in cardiac output ( approximately 60%) during pregnancy. Myocardial eNOS (21 +/- 4%), phosphorylated eNOS (19 +/- 3%), and SOD-1 (61 +/- 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10(-4) mol/l) decreased MVO(2) in a nitric oxide-dependant manner (by 24 +/- 1.3% in controls and 34 +/- 2.2% at 60D; by 21 +/- 1.1% in controls and 29 +/- 1.1 at 60D; and by 22 +/- 2.5% in controls and 26 +/- 1.0% at 60D, respectively). Arterioles from pregnant dogs showed increased flow-dependant dilation in response to increased shear stress and larger passive diameter. Nitrite production was stimulated by bradykinin and carbachol in microvessels in vitro; pregnancy enhanced nitrite release. Myocardial eNOS, phosphorylated eNOS, and SOD-1 protein expression are increased during pregnancy, and this increase is associated with enhanced nitric oxide-dependant control of MVO(2). Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.
我们研究了心脏内皮型一氧化氮合酶（eNOS）在孕期耦合心肌耗氧量（MVo₂）和氧输送的能力。使用超声心动图对清醒犬在妊娠前、妊娠40天、50天和60天（60D）以及产后约14天进行研究。通过免疫印迹法测定左心室eNOS、磷酸化eNOS以及铜锌超氧化物歧化酶（CuZnSOD或SOD-1）。体外测量左心室组织样本对递增剂量缓激肽、马来酸依那普利和氨氯地平的MVO₂。我们检测了冠状动脉小动脉的被动直径变化和流量依赖性小动脉扩张。超声心动图显示孕期心输出量增加（约60%）。在妊娠60天时，心肌eNOS（21±4%）、磷酸化eNOS（19±3%）和SOD-1（61±2.7%）蛋白水平显著升高。缓激肽、马来酸依那普利和氨氯地平（10⁻⁴mol/L）以一氧化氮依赖的方式降低MVO₂（对照组降低24±1.3%，60D时降低34±2.2%；对照组降低21±1.1%，60D时降低29±1.1%；对照组降低22±2.5%，60D时降低26±1.0%）。妊娠犬的小动脉对增加的剪切应力表现出增强的流量依赖性扩张，且被动直径更大。体外实验中，缓激肽和卡巴胆碱刺激微血管产生亚硝酸盐；妊娠增强了亚硝酸盐释放。孕期心肌eNOS、磷酸化eNOS和SOD-1蛋白表达增加，且这种增加与一氧化氮依赖的MVO₂控制增强有关。因此，eNOS和SOD-1的增加促进了孕期心脏氧输送与效率的耦合。
