Effect of nitric oxide on local vascular regulation in vivo perfusion system of rat.

1)我们改进了大鼠血管灌流中一氧化氮（NO）的测定系统。用NO直接测量系统（Model No.501或Model MES-100）和每个NO选择性电极测量NO。使用NO标准溶液为两种型号中的每个电极绘制校准曲线。电极检测到超过0.06 nmole的NO。2）乙酰胆碱（ACh）剂量依赖性地产生NO和伴随的血管舒张系统。NO合成酶抑制剂阻断NO的释放，但ACh的舒张作用仍然存在。在L-NMMA和TEA的存在下或去内皮化的情况下，ACh引起的灌注压（PP）下降几乎被消除。缓激肽（BK）也可诱导NO的释放，并对PP产生双相效应，低浓度时减少，高浓度时增加。L-NMMA和TEA均能阻断BK引起的PP降低，在L-NMMA和TEA共同存在时，这些结果表明，ACh和BK通过内皮细胞释放NO和钾通道依赖性机制诱导血管舒张。3）使用该系统在高血压模型（SHR）和正常对照（WKY）中研究了去甲肾上腺素（NE）反应时血管收缩引起的NO释放4 - 16周龄的大鼠。我们发现NO释放和PP增加之间的显着相关性在WKY的血管收缩在4 - 16周龄，但没有在年龄匹配的SHR。在WKY的NOx排出量在4周龄大于在年龄匹配的SHR，并逐渐减少，从4到16周龄的年龄。而SHR的NO释放量在4 ~ 12周龄无明显变化，16周龄时下降至与同龄WKY相当的水平，表明WKY和SHR的NO释放量均随增龄而下降，提示SHR血管内皮细胞NO生成功能异常，可能与血管收缩有关。

1) We improved nitric oxide (NO) measuring system in the vascular perfusion of rat. NO was measured with NO direct-measuring systems (Model No.501, or Model MES-100) with each NO selective electrode. A calibration curve was prepared for each electrode in both Models using an NO standard solution. The electrodes detected more than 0.06 nmole of NO.2) Acetylcholine (ACh) dose-dependently produced NO and concomitant vasodilation in the system. NO synthase inhibitor blocked NO release, but the vasodilation by ACh remained. The decrease in perfusion pressure (PP) in response to ACh was almost abolished in the presence of both L-NMMA and TEA or with deendothelialization. Bradykinin (BK) also induced NO release and biphasic effects on PP, which decreased with a lower concentration of BK and increased with a higher concentration. L-NMMA and TEA each abolished the decrease in PP induced by BK.In the presence of both L-NMMA and TEA, PP increased in response to BK.These results suggest that ACh and BK induce vasodilation through NO release and potassium channel dependent mechanism via endothelium.3) NO release by vasoconstriction in response to norepinephrine (NE) was investigated using this system in a model of hypertension (SHR) and normal control (WKY) rats between 4 and 16-week age. We found a significant correlation between NO release and the increase in PP by vasoconstriction in WKY between 4 and 16-week age, but not in age-matched SHR.NOx excretion in WKY was greater at 4-week age than that in age-matched SHR, and gradually decreased with aging from 4 to 16-week age. Whereas, NOx excretion in SHR did not change from 4 to 12-week age, and then decreased at 16-week age to a level of that in age-matched WKY.These results show that NO release decreased with age in both WKY and SHR, and suggest that there might be abnormal endothelial function of NO production to vasoconstriction in SHR.