A new role of NO on the accelerating effect of oxygen supply to tissue

应用双斑点显微光谱分析技术，观察硝酸甘油对大鼠肝微循环中氧释放的影响。硝酸甘油可显著增加流经血窦的红细胞的氧含量。单位长度血窦的血氧饱和度差异显著增大，而红细胞速度、血色素(Hb)浓度、流入血窦的氧合血红蛋白以及用激光组织血流仪测量的局部肝脏血流量无明显变化。在用无Hb含氧缓冲液灌流的离体肝中，测得的肝脏耗氧量无明显变化。硝酸异山梨酯表现出类似的效果，但速度较慢。这些发现表明，硝酸甘油和硝酸异山梨酯在不显著增加组织血流量的情况下，增加了红细胞的O2释放。体外研究表明，硝酸甘油处理的大鼠血液中O2亲和力显著降低。它不含单独与Hb一个亚基的结合。在器官循环过程中，NO-血红素铁-近端组氨酸键的断裂或拉伸可能引起O2亲和力的下降，而肺内O2亲和力的恢复是通过恢复该键来实现的。这些结果应该是当细胞因子在炎症等事件中诱导血管系统中没有合成酶时起作用的。

The effect of nitroglycerin on oxygen (O2) release in microcirculation was investingated by examining single, unbranched hepatic sinusoids of rats using dual-spot microspectroscopy. Nitroglycerin significantly increased O2 selease from erythrocytes flowing in the sinusoids. Differences in O2 saturation of hemoglobin per unit length of the sinusoid were significantly enhanced, while there were no significant changes in erythrocyte velocity, hemoglobin (Hb) concentration, and oxyhemoglobin flow into the sinusoids, as well as regional hepatic blood flow measured with a laser tissue blood flow meter. No change was noted for hepatic O2 consumption measured in isolated liver perfused with Hb-free oxygenated buffer. Isosorbide denitrate showed a similar but slower effect. These findings suggest that nitroglycerin and isosorbide dinitrate enhance O2 release from erythrocytes without significantly increasing tissue blood flow. In vitro study revealed O2 affinity was significantly decreased in blood taken from rats treated with nitroglycerin. It contained NO bound to Hb a subunit alone. It is possible that breaking or stretching of the NO heme iron-proximal histidine bond during organ circulation triggered the decrease in O2 affinity, while the O2 affinity was recovered in lung by restoring the bond. These results should operate when cytokines induce NO synthase in vascular system during such events as inflammation.