Department of Physiology, Georgia Regents University, Augusta, Georgia;
Am J Physiol Heart Circ Physiol. 2013 Dec;305(12):H1726-35. doi: 10.1152/ajpheart.00535.2013. Epub 2013 Oct 4.
The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N(ω)-nitro-l-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen-glucose deprivation experienced a similar loss of myogenic tone. Inhibition of peroxynitrite parent radicals significantly improved the myogenic tone. Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham operation rather than the nonischemic side should be used as a control in preclinical stroke studies.
肌源性反应对于维持血管阻力以在压力波动期间实现恒定灌注至关重要。据报道，在中风后，缺血和非缺血半球的脑血流减少。缺血再灌注损伤和由此产生的氧化应激会损害缺血半球的肌源性反应。然而，缺血再灌注影响非缺血侧的机制仍未确定。本研究的目的是确定缺血再灌注损伤对两个半球脑血管的肌源性反应的影响，以及由于过氧化物亚硝酸根产生导致的蛋白质硝化是否是张力丧失的潜在机制。雄性 Wistar 大鼠接受假手术或 30 分钟大脑中动脉闭塞/45 分钟再灌注。大鼠在再灌注时给予生理盐水、过氧化物亚硝酸根分解催化剂 5,10,15,20-四（4-磺基苯）卟啉铁（III）或硝化抑制剂表儿茶素。从另一组对照大鼠中分离出的大脑中动脉暴露于体外氧葡萄糖剥夺，并与糖蛋白 91 tat（NADPH 氧化酶抑制剂）或 N（ω）-硝基-L-精氨酸甲酯一起。测定肌源性张力和硝基酪氨酸水平。与假手术组相比，缺血再灌注损伤损害了两个半球血管的肌源性张力（P < 0.001）。暴露于体外氧葡萄糖剥夺的血管经历了类似的肌源性张力丧失。过氧化物亚硝酸根母体自由基的抑制显著改善了肌源性张力。过氧化物亚硝酸根清除或硝化抑制改善了缺血（P < 0.001 和 P < 0.05）和非缺血（P < 0.01 和 P < 0.05）半球血管的肌源性张力。与假手术组相比，两个半球的硝化均显著增加，并用表儿茶素治疗得到正常化。总之，缺血再灌注损伤通过硝化损害了两个半球的血管反应性。我们建议在临床前中风研究中，应将假手术而不是非缺血侧作为对照。
