Departamento de Fisiologia, Facultad de Medicina, Granada, Spain.
J Physiol Pharmacol. 2010 Jun;61(3):325-32.
The vasoconstrictor effect of hydrogen peroxide (H(2)O(2)) on isolated perfused rat kidney was investigated. H(2)O(2) induced vasoconstriction in the isolated rat kidney in a concentration-dependent manner. The vasoconstrictor effects of H(2)O(2) were completely inhibited by 1200 U/ml catalase. Endothelium-removal potentiated the renal response to H(2)O(2). The H(2)O(2) dose-response curve was not significantly modified by administration of the NO inhibitor L-NAME (10(-4) mol/l), whereas it was increased by the non-specific inhibitor of K+-channels, tetraethylammonium (3.10(-3) mol/l). Separately, removal of extracellular Ca(2+), administration of a mixture of calcium desensitizing agents (nitroprusside, papaverine, and diazoxide), and administration of a protein kinase C (PKC) inhibitor (chelerythrine, 10(-5) mol/l) each significantly attenuated the vasoconstrictor response to H(2)O(2), which was virtually suppressed when they were performed together. The pressor response to H(2)O(2) was not affected by: dimethyl sulfoxide (7.10(-5) mol/l) plus mannitol (3.10(-5) mol/l); intracellular Ca(2+) chelation using BAPTA (10(-5) mol/l); calcium store depletion after repeated doses of phenylephrine (10(-5) g/g kidney); or the presence of indomethacin (10(-5) mol/l), ODYA (2.10(-6) mol/l) or genistein (10(-5) mol/l). We conclude that the vasoconstrictor response to H(2)O(2) in the rat renal vasculature comprises the following components: 1) extracellular calcium influx, 2) activation of PKC, and 3) stimulation of pathways leading to sensitization of contractile elements to calcium. Moreover, a reduced pressor responsiveness to H(2)O(2) in female kidneys was observed.
研究了过氧化氢(H₂O₂)对分离灌注大鼠肾脏的血管收缩作用。H₂O₂以浓度依赖性方式诱导大鼠肾脏血管收缩。1200U/ml 过氧化氢酶完全抑制 H₂O₂ 的血管收缩作用。内皮去除增强了肾脏对 H₂O₂ 的反应。NO 抑制剂 L-NAME(10⁻⁴mol/L)给药后,H₂O₂剂量反应曲线没有显著改变,而非特异性 K⁺通道抑制剂四乙铵(3.10⁻³mol/L)则增加了 H₂O₂的剂量反应曲线。此外,去除细胞外 Ca²⁺,给予钙敏感受体抑制剂混合物(硝普钠、罂粟碱和二氮嗪),以及给予蛋白激酶 C(PKC)抑制剂(桔皮素,10⁻⁵mol/L),均可显著减弱对 H₂O₂的血管收缩反应,当它们一起进行时,几乎抑制了这种反应。H₂O₂的升压反应不受以下因素影响:二甲基亚砜(7.10⁻⁵mol/L)加甘露醇(3.10⁻⁵mol/L);使用 BAPTA(10⁻⁵mol/L)螯合细胞内 Ca²⁺;反复给予苯肾上腺素(10⁻⁵g/g 肾脏)后钙储存耗竭;或存在吲哚美辛(10⁻⁵mol/L)、ODYA(2.10⁻⁶mol/L)或金雀异黄素(10⁻⁵mol/L)。我们得出结论,大鼠肾血管对 H₂O₂的血管收缩反应包括以下成分:1)细胞外钙内流,2)PKC 激活,3)刺激导致收缩成分对钙敏感的途径。此外,还观察到雌性肾脏对 H₂O₂的升压反应降低。