Potentiated endothelium-derived hyperpolarizing factor-mediated dilations in cerebral arteries following mild head injury

Evidence in the literature suggests that endothelium-derived hyperpolarizin g factor (EDHF) may act in a compensatory manner such that during condition s of compromised nitric oxide (NO), EDHF serves as a back-up mechanism. Giv en that constitutive NO synthase is chronically downregulated after head tr auma, we tested the hypothesis that EDHF is potentiated following injury. M ale adult rats were subjected to either sham injury (n = 27) or mild contro lled cortical impact (CCI) injury (n = 26). Branches of the middle cerebral artery (MCA) directly within the contusion site were harvested either 1 or 24 h later, pressurized to 60 mm Hg in a vessel chamber and allowed to dev elop spontaneous tone. Relaxation to luminal application of adenosine triph osphate (ATP) was similar in all groups. Relaxation to ATP in the presence of L-NAME (N(G)-nitro-L-arginine methyl ester) and indomethacin was similar in all groups except for vessels isolated at 24 h following mild CCI injur y. In this case, L-NAME and indomethacin had no effect on the ATP-mediated dilation. The ATP-mediated dilation in L-NAME and indomethacin-treated MCA branches was inhibited by charybdotoxin, an inhibitor of large conductance Ca2+-sensitive K+ channels. These findings suggest that there is a signific ant potentiation of the EDHF-mediated dilation to ATP in cerebral arteries isolated at 24 h following mild CCI injury.