Abstract 150: Protein Nitration Impairs Myogenic Reactivity of Cerebral Vessels in Both Ischemic & Non-ischemic Hemispheres
Cerebrovascular autoregulation is critical to maintain constant perfusion during ischemic brain injury. It is known that ischemia/reperfusion (I/R) injury and resulting oxidative stress impair vessel reactivity in ischemic (IS) side. Yet the behavior of vessels in nonischemic (NIS) side is still unexplored.
Hypothesis: I/R injury impairs myogenic tone of vessels in both IS & NIS hemispheres via increased peroxynitrite (ONOO- ) generation.
Methods: Male Wistar rats (n=8) were subjected to sham or 30 min middle cerebral artery occlusion (MCAO)/45 min reperfusion. Rats were administered saline, ONOO- decomposition catalyst FeTPPs (20 mg/kg) or nitration inhibitor epicatechin (30mg/kg) at reperfusion. In another set of animals, MCA isolated from control rats were exposed to ex-vivo hypoxia with and without gp-91 tat (NADPH oxidase inhibitor 1μM), L-NAME (0.3 mM) and Catalase (1000 u/ml) during reoxygenation. The tone of MCAs across the pressure range was measured using pressurized arteriograph. Nitrotyrosine levels in MCAs from both hemispheres were evaluated using immunoblotting.
Results: I/R injury impaired myogenic tone of vessels in both IS & NIS hemispheres albeit to a different degree. Vessels exposed to ex-vivo hypoxia experienced similar loss of myogenic tone. Inhibiting ONOO- by FeTPPs and nitration by epicatechin restored myogenic tone of vessels from both hemispheres back to normal, while inhibiting hydrogen peroxide had no effect. Nitration was significantly increased in both IS (**p<0.01) & NIS hemispheres (*<p0.05) vs sham. Treatment with epicatechin efficiently reduced the extent of nitration back to normal.
Conclusion: These results support our hypothesis that I/R injury impairs myogenic tone in BOTH IS and NIS hemispheres and protein nitration due to increased ONOO- production is one of the underlying mechanisms of loss of tone.(† p<0.001, * p< 0.05 vs Sham, # p<0.001 vs IS, *p<0.05,***p<0.001 vs NIS)
- © 2012 by American Heart Association, Inc.