Sethi S, Singh M P, Dikshit M
Pharmacology Division, Central Drug Research Institute, Lucknow, India.
Blood. 1999 Jan 1;93(1):333-40.
Polymorphonuclear leukocytes (PMNLs), nitric oxide (NO), calcium, and free radicals play an important role in hypoxia/ischemia and reoxygenation injury. In the present study, NO donors, sodium nitroprusside (SNP), and diethylamine-NO (DEA-NO) at low concentrations (10 and 100 nmol/L) potentiated, while higher (10 micromol/L to 10 mmol/L) concentrations inhibited free radical generation response in the rat PMNLs. Free radical generation response was found to be significantly augmented when hypoxic PMNLs were reoxygenated (hypoxia-reoxygenation [H-R]). This increase in free radical generation after reoxygenation or SNP (10 nmol/L) was blocked in the absence of extracellular calcium. SNP (10 nmol/L) or H-R-mediated increases in the free radical generation were prevented by the pretreatment of PMNLs with NO scavenger (hemoglobin), the polyadenine diphosphate (ADP)-ribosylation synthase inhibitor (benzamide) or the calcium channel antagonist (felodipine). A significant augmentation in the nitrite and intracellular calcium levels was observed during hypoxia. Hemoglobin pretreatment also blocked the increase in intracellular calcium levels due to SNP (10 nmol/L) or hypoxia. Thus, increased availability of NO during SNP treatment or H-R, may have led to an ADP-ribosylation-mediated increase in intracellular calcium, thereby increasing the free radical generation from the rat PMNLs.
多形核白细胞（PMNLs）、一氧化氮（NO）、钙和自由基在缺氧/缺血及再氧合损伤中起重要作用。在本研究中，低浓度（10和100 nmol/L）的NO供体硝普钠（SNP）和二乙胺 - NO（DEA - NO）可增强大鼠PMNLs中的自由基生成反应，而较高浓度（10 μmol/L至10 mmol/L）则抑制该反应。当缺氧的PMNLs进行再氧合（缺氧 - 再氧合[H - R]）时，发现自由基生成反应显著增强。在无细胞外钙的情况下，再氧合或SNP（10 nmol/L）后自由基生成的这种增加被阻断。用NO清除剂（血红蛋白）、多聚腺苷二磷酸（ADP） - 核糖基化合成酶抑制剂（苯甲酰胺）或钙通道拮抗剂（非洛地平）预处理PMNLs可防止SNP（10 nmol/L）或H - R介导的自由基生成增加。在缺氧期间观察到亚硝酸盐和细胞内钙水平显著升高。血红蛋白预处理也阻断了由于SNP（10 nmol/L）或缺氧导致的细胞内钙水平升高。因此，在SNP处理或H - R期间NO可用性增加，可能导致ADP - 核糖基化介导的细胞内钙增加，从而增加大鼠PMNLs中的自由基生成。
