Background: Myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow was reported in ischemic (IS) and nonischemic (NIS) hemispheres after stroke. Ischemia/reperfusion injury and resulting oxidative stress impair myogenic response in IS hemisphere. Yet, the mechanism by which ischemia/reperfusion affects the NIS side is still undetermined. Goal: 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. Methods: Male Wistar-rats were subjected to sham or 30 min middle-cerebral-artery (MCA) occlusion/45 min reperfusion. Rats were administered saline, peroxynitrite decomposition catalyst FeTPPs or nitration inhibitor epicatechin at reperfusion. MCAs isolated from another set of control rats were exposed to ex-vivo oxygen-glucose- deprivation (OGD) with & without gp-91 tat (NOX inhibitor) or L-NAME. Myogenic tone and nitrotyrosine levels were determined. Results: Ischemia/reperfusion injury impaired myogenic tone of vessels in both hemispheres compared to sham (***p<0.001). Vessels exposed to ex-vivo OGD experienced similar loss of myogenic tone. Inhibiting peroxynitrite parent radicals significantly improved myogenic tone. Scavenging peroxynitrite or inhibiting nitration improved myogenic tone of vessels from IS (***p<0.001,*p<0.05 respectively) and NIS hemispheres (**p<0.01, *p<0.05 respectively). Nitration was significantly increased in both hemispheres vs sham and was normalized with epicatechin treatment. Conclusion: Ischemia/reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham animals rather than nonischemic side should be used as a control in preclinical stroke studies.
- contralateral hemisphere
- ischemia/reperfusion injury
- myogenic tone
- Copyright © 2013, American Journal of Physiology - Heart and Circulatory Physiology