We previously demonstrated that rapid posthypothermic rewarming in noninjured animals was capable of damaging cerebral arterioles both at endothelial and smooth muscle levels. Such adverse consequences could be prevented with antioxidants, suggesting the involvement of free radicals. In this study, we further investigate the mechanisms associated with free radicals production by using two radical scavengers, superoxide dismutase (SOD) and catalase. Employing rats, the cerebral vascular response was evaluated at 2, 3, and 4 hours after onset of hypothermia. Before rapid rewarming, SOD treatment, but not catalase, preserved the NO-mediated dilation induced by acetylcholine (ACh). On the contrary, catalase preserved the hypercapnia-induced relaxation of the smooth muscle cells, whereas SOD offered only partial protection. Adding SOD to catalase treatment offered no additional benefit. These results suggest that rapid posthypothermic rewarming impairs ACh- and hypercapnia-induced vasodilation through different subcellular mechanisms. In the case of diminished vascular response to ACh, it appears to act on the endothelial front primarily by superoxide anions, as evidenced by its full preservation after SOD treatment. In terms of impaired dilation to hypercapnia, hydrogen peroxide and/or its derivatives are the likely candidates in targeting the smooth muscle cells. The partial protection of SOD to hypercapnia-induced dilation is believed to be the reduced amount of superoxide that would otherwise spontaneously dismutate to produce hydrogen peroxide. Although SOD exerts some indirect influence on the hydrogen peroxide production downstream, catalase apparently has no influence on upstream superoxide production.
Keywords: acetylcholine and hypercapnia-induced vasodilation; pial vasculature; response to rapid posthypothermic rewarming; the utility of superoxide dismutase and catalase.