Exercise training restores impaired dilator responses of cerebral arterioles during chronic exposure to nicotine.

Our goal was to determine whether exercise training (ExT) alleviates impaired nitric oxide synthase (NOS)-dependent dilation of pial arterioles during chronic exposure to nicotine. We measured dilation of cerebral (pial) arterioles in sedentary and exercised control and nicotine-treated (2 mg·kg(-1)·day(-1) for 4 wk via an osmotic minipump) rats to an endothelial NOS (eNOS)-dependent (ADP), a neuronal NOS (nNOS)-dependent [N-methyl-D-aspartic acid (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we harvested brain tissue from sedentary and exercised control and nicotine-treated rats to measure the production of superoxide anion and measured superoxide dismutase-1 (SOD-1) protein in cerebral microvessels using Western blot. We found that eNOS-and nNOS-dependent, but not NOS-independent, vasodilation was impaired in nicotine-treated compared with control rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased, and SOD-1 protein decreased, in rats treated with nicotine compared with control rats. Further, although ExT did not significantly affect eNOS- or nNOS-dependent vasodilation in control rats, ExT restored impaired eNOS- and nNOS-dependent responses in nicotine-treated rats. In addition, the increase in superoxide anion production observed in nicotine-treated rats was reduced by ExT, and SOD-1 protein was increased in nicotine-treated rats by ExT. We suggest that ExT restores impaired NOS-dependent dilation of pial arterioles during chronic exposure to nicotine by a mechanism related to the formation of superoxide anion.