Endothelial function regulating migration of leukocytes to tissues

独立于肥大细胞，内源性NO的生理作用是防止血管内皮氧化应激和随后的白细胞粘附和迁移，而肥大细胞在免疫复合物介导的白细胞粘附和迁移中起重要作用。因此，接下来我们研究了增加超氧化物或减少NO的现象。血管紧张素II （Ang II）的灌注使大鼠肠系膜微循环血流停止，但连续的血流循环发生。超氧化物歧化酶（SOD）显著延缓了angii的停止，并使连续的再流更早地恢复。通过荧光素类似物的化学发光方法观察到，Ang II和肠系膜动脉之间的急性反应诱导立即产生超氧化物。急性血管超氧化物的产生有助于体外血管收缩，因为它被SOD显著减弱。急性超氧化物产生作用可能是针对Ang II的，因为SOD对去甲肾上腺素的这种显著修饰未被观察到。高血压盐敏感的Dahl大鼠肾动脉EDCF合成/释放的诱导导致了乙酰胆碱内皮依赖性松弛受损。l -精氨酸作为一氧化氮合酶抑制剂的底物，可以减弱钠潴留和高血压的发展，从而导致肾动脉EDCF合成减少。我们对离体大鼠心脏进行了短暂的全身缺血，然后再灌注。热缺血后心肌细胞在再灌注时出现凋亡，冷缺血后心肌细胞无凋亡。Caspase抑制剂能改善左心室分式缩短，减少心肌细胞凋亡和缺血再灌注引起的梗死面积。我们将研究超氧化物对细胞凋亡的影响。

Independently to mast cells, endogenous NO is physiologically operating to prevent vascular endothelium from oxidative stress and subsequent leukocyte adhesion and emigration, while mast cells play an essential role in the immune complex-mediated leukocyte adhesion and emigration. Thus next we examined the phenomenon to increase superoxide or to decrease NO.Superfusion of angiotensin II (Ang II) ceased blood flow in rat mesenteric microcirculation, however, successive reflow occurred. Superoxide dismutase (SOD) significantly delayed the stoppage by Ang II and restored the successive reflow earlier. The acute reaction between Ang II and mesenteric artery induced immediate superoxide production when observed by a chemiluminescence method using Cypridina luciferin analog. The acute vascularsuperoxide production on addition of Ang II contributed to in vitro vascular contraction as it was significantly attenuated by SOD.The acute superoxide producing effect is likely to be specific to Ang II, because such significant modification by SOD was not observed for norepinephrine.Impaired endothelium-dependent relaxation to acetylcholine is caused in part by induction of EDCF synthesis/release in renal arteries of hypertensivesalt-sensitive Dahl rats. L-Arginine, a substrate of nitric oxide synthase inhibitor, can attenuate sodium retention and development of hypertension, which lead to a decrease in EDCF synthesis in renal arteries.We performed transient global ischemia in isolated rat hearts, followed by reperfusion. Cardiomyocytes showed apoptosis on reperfusion after warm ischemia, but not after cold ischemia. Caspase inhibitor can improve fractional shortening of the-left ventricle and to reduce cardiomyocyte apoptosis and the infarcted area induced by ischemia-reperfusion. We will examine effect of superoxide on the apoptosis.