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

1)改进大鼠血管灌注一氧化氮（NO）测量系统。采用NO直接测量系统（型号NO .501，或型号MES-100）和每个NO选择电极测量NO。使用NO标准溶液对两种型号的每个电极制备校准曲线。电极在系统中检测到超过0.06 nmol的2 -乙酰胆碱（ACh）剂量依赖性产生的NO和伴随的血管舒张。NO合成酶抑制剂阻断NO的释放，但乙酰胆碱的血管舒张作用仍然存在。在L-NMMA和TEA存在或去内皮化的情况下，乙酰胆碱引起的灌注压（PP）下降几乎被消除。缓激素（BK）还能诱导NO释放，并对PP产生双相效应，其浓度随BK浓度的降低而降低，随浓度的升高而升高。L-NMMA和TEA均能消除BK引起的PP下降。在L-NMMA和TEA存在的情况下，PP对BK的反应增加。这些结果表明，ACh和BK通过内皮细胞释放NO和钾通道依赖机制诱导血管舒张。3)在4 ~ 16周龄的高血压（SHR）和正常对照（WKY）大鼠模型中，应用该系统研究了血管收缩对去甲肾上腺素（NE）的NO释放。我们发现在4 - 16周龄的WKY中NO释放与血管收缩引起的PP增加有显著相关性，但在年龄匹配的SHR中没有。4周龄时WKY的NOx排泄量大于同龄SHR， 4 ~ 16周龄随年龄增长逐渐降低。4 ~ 12周龄时，SHR的NOx排泄量变化不大，16周龄时，NOx排泄量下降至与年龄匹配的WKY水平。这些结果表明，在WKY和SHR中，NO的释放量随年龄的增长而下降，提示SHR中NO的产生对血管收缩可能存在异常的内皮功能。

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.