Modulation of gap junction-dependent arterial relaxation by ascorbic acid

Aims: To investigate whether ascorbic acid ( AA) can influence endothelium-dependent relaxation by modulating the spread of endothelial hyperpolarization through the arterial wall via gap junctions. Methods: Force development and membrane potential were monitored by myography and sharp electrode techniques in isolated rabbit iliac arteries. Results: AA prevented the ability of the gap junction blocker 2-aminoethoxydiphenyl borate to inhibit endothelium-dependent relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid in the presence of nitric oxide (NO) synthase and cyclooxygenase blockade. AA also prevented the ability of a connexin-mimetic peptide targeted against Cx37 and Cx40 ( (37,40) Gap 26) to attenuate the transmission of endothelial hyperpolarization to subintimal smooth muscle, and a peptide targeted against Cx43 ( (43) Gap 26) to attenuate the spread of subintimal hyperpolarization to subadventitial smooth muscle and the associated mechanical relaxation. Parallel studies with endothelium-denuded preparations demonstrated that AA and cyclopiazonic acid both depressed relaxation evoked by the NO donor MAHMA NONOate. Conclusions: The data suggest that AA can modulate arterial function through a previously unrecognized ability to preserve electrotonic signalling via myoendothelial and homocellular smooth muscle gap junctions under conditions where cell coupling is depressed. Underlying mechanisms do not involve amplification of `residual' NO activity by AA.