Cardiovascular Pharmacology Unit, Central Drug Research Institute, Lucknow, India.
Free Radic Res. 2009 Dec;43(12):1195-204. doi: 10.3109/10715760903247256.
The present study explores expression of NOS and pro-inflammatory cytokines, NOS catalysis and NO mediated modulation of oxidative response and apoptosis in neutrophils from spontaneously hypertensive rats (SHR). Neutrophils from SHR showed approximately 3-fold increments in iNOS expression, 1.5-fold increments in nOS expression and calcium independent NOS catalysis, whereas GTPCH expression was unaltered. Although phagocytic potential was comparable, neutrophils from SHR demonstrated augmented oxidative burst, which was reduced by NOS inhibition or in the presence of NO scavenger. SHR neutrophils also exhibited enhanced MPO catalysis and Ca(2+) levels. Levels of TNF-alpha and IFN-gamma were comparable, but IL-1beta and CRP levels in SHR plasma were (p<0.05) elevated. This study evidenced significantly enhanced expression of IL-1beta in SHR neutrophils whereas those of TNF-alpha and IFN-gamma were unaltered. Moreover neutrophils from SHR exhibited (p<0.01) delayed apoptotic response and sustained NO generation, as evident from elevated nitrite levels in neutrophil culture supernatant above the control levels. Results obtained indicate an augmented NO generation from neutrophils during hypertension which might fortify their attribute to the oxidative and inflammatory stress in SHR, emphasizing the importance of neutrophils in hypertension.
本研究探讨了自发性高血压大鼠（SHR）中性粒细胞中 NOS 和促炎细胞因子的表达、NOS 催化以及 NO 对氧化反应和细胞凋亡的调节作用。SHR 中性粒细胞的 iNOS 表达增加了约 3 倍，nNOS 表达增加了 1.5 倍，且钙非依赖性 NOS 催化增强，而 GTPCH 表达不变。尽管吞噬能力相当，但 SHR 中性粒细胞的氧化爆发增强，NOS 抑制或存在 NO 清除剂时可减少氧化爆发。SHR 中性粒细胞还表现出增强的 MPO 催化和 Ca(2+) 水平。TNF-α和 IFN-γ的水平相当，但 SHR 血浆中的 IL-1β和 CRP 水平升高（p<0.05）。这项研究表明 SHR 中性粒细胞中 IL-1β的表达显著增强，而 TNF-α和 IFN-γ的表达不变。此外，SHR 中性粒细胞表现出（p<0.01）延迟的凋亡反应和持续的 NO 生成，这从中性粒细胞培养上清液中硝酸盐水平高于对照水平就可以看出。研究结果表明，高血压期间中性粒细胞中 NO 的生成增加，这可能增强了它们在 SHR 氧化和炎症应激中的属性，强调了中性粒细胞在高血压中的重要性。
