University of Belgrade, Institute for Biological Research Sinisa Stankovic, Department of Physiology, Belgrade, Serbia.
Br J Pharmacol. 2009 Dec;158(8):1932-41. doi: 10.1111/j.1476-5381.2009.00490.x.
The effects of hydrogen peroxide (H(2)O(2)) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca(2+))-induced] and the effect of such treatment on anti-oxidative enzyme activities.
Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca(2+) (6 mM) and treated with H(2)O(2) (2 microM-3 mM) over 2 h. Anti-oxidative enzyme activities (manganese superoxide dismutase-MnSOD, copper-zinc superoxide dismutase-CuZnSOD, catalase-CAT, glutathione peroxidase-GSHPx and glutathione reductase-GR) in H(2)O(2)-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca(2+)-induced contractions, without treatment with H(2)O(2). The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H(2)O(2)-mediated relaxation was explored.
H(2)O(2) caused concentration-dependent relaxation of both spontaneous and Ca(2+)-induced uterine contractions. After H(2)O(2) treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca(2+)-induced rat uteri) were decreased. N(omega)-nitro-L-arginine methyl ester antagonized the effect of H(2)O(2) on Ca(2+)-induced contractions. H(2)O(2)-induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4-aminopyridine and glibenclamide, with the last compound being the least effective.
H(2)O(2) induced dose-dependent relaxation of isolated rat uteri mainly via changes in voltage-dependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti-oxidative pathways may lead to new approaches to the management of dysfunctional uteri.
过氧化氢（H₂O₂）对子宫平滑肌的影响尚未得到充分研究。我们研究了外源性过氧化氢对大鼠子宫收缩活动（自发性和钙离子（Ca²⁺）诱导）的作用及其机制，以及这种处理对抗氧化酶活性的影响。
从处女 Wistar 大鼠中分离出子宫，将其悬挂在器官浴中。子宫允许自发收缩或在 Ca²⁺（6mM）存在下收缩，并在 2 小时内用 H₂O₂（2μM-3mM）处理。将 H₂O₂处理后的子宫中的抗氧化酶活性（锰超氧化物歧化酶-MnSOD、铜锌超氧化物歧化酶-CuZnSOD、过氧化氢酶-CAT、谷胱甘肽过氧化物酶-GSHPx 和谷胱甘肽还原酶-GR）与子宫立即冷冻后的活性进行比较，子宫立即冷冻是在没有用 H₂O₂处理的情况下进行的，或者是在自发收缩或 Ca²⁺诱导收缩时进行的。还探索了抑制剂（心得安、亚甲蓝、L-NAME、四乙铵、格列本脲和 4-氨基吡啶）对 H₂O₂介导的松弛的影响。
H₂O₂引起自发性和 Ca²⁺诱导的子宫收缩的浓度依赖性松弛。H₂O₂处理后，GSHPx 和 MnSOD 活性增加，而 CuZnSOD 和 GR（在 Ca²⁺诱导的大鼠子宫中）减少。N（ω）-硝基-L-精氨酸甲酯拮抗 H₂O₂对 Ca²⁺诱导收缩的作用。H₂O₂诱导的松弛不受心得安的影响，被亚甲蓝增强，被四乙铵、4-氨基吡啶和格列本脲拮抗，后一种化合物的作用最弱。
H₂O₂诱导的离体大鼠子宫的浓度依赖性松弛主要通过改变电压依赖性钾通道。通过刺激抗氧化途径减少活性氧的产生可能为治疗功能失调的子宫提供新的方法。
