Endothelium‐dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis?

Abstract

An endothelium-derived hyperpolarizing factor (EDHF) that is distinct from nitric oxide (NO) and prostanoids has been widely hypothesized to hyperpolarize and relax vascular smooth muscle following stimulation of the endothelium by agonists. Candidates as diverse as K(+) ions, eicosanoids, hydrogen peroxide and C-type natriuretic peptide have been implicated as the putative mediator, but none has emerged as a 'universal EDHF'. An alternative explanation for the EDHF phenomenon is that direct intercellular communication via gap junctions allows passive spread of agonist-induced endothelial hyperpolarization through the vessel wall. In some arteries, eicosanoids and K(+) ions may themselves initiate a conducted endothelial hyperpolarization, thus suggesting that electrotonic signalling may represent a general mechanism through which the endothelium participates in the regulation of vascular tone.