title: Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor.
abstract: The nature of the vasodilator endothelium-derived hyperpolarizing factor (EDHF) is controversial, putatively involving diffusible factors and/or electrotonic spread of hyperpolarization generated in the endothelium via myoendothelial gap junctions (MEGJs). In this study, we investigated the relationship between the existence of MEGJs, endothelial cell (EC) hyperpolarization, and EDHF-attributed smooth muscle cell (SMC) hyperpolarization in two different arteries: the rat mesenteric artery, where EDHF-mediated vasodilation is prominent, and the femoral artery, where there is no EDHF-dependent relaxation. In the rat mesenteric artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization of both ECs and SMCs, and characteristic pentalaminar MEGJs were found connecting the two cell layers. In contrast, in the femoral artery, ACh evoked hyperpolarization in only ECs but not in SMCs, and no MEGJs were present. Selective hyperpolarization of ECs or SMCs evoked hyperpolarization in the other cell type in the mesenteric artery but not in the femoral artery. Disruption of gap junctional coupling using the peptide Gap 27 markedly reduced the ACh-induced hyperpolarization in SMCs, but not in ECs, of the mesenteric artery. These results show that transfer of EC hyperpolarization or of a small molecule to SMCs through MEGJs is essential and sufficient to explain EDHF.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.forename: Harold A
authors.initials: HA
authors.lastname: Coleman
authors.forename: Caryl E
authors.initials: CE
authors.lastname: Hill
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D017630:Connexins / Q000494:pharmacology; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005263:Femoral Artery / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D017629:Gap Junctions / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D009131:Muscle, Smooth, Vascular / Q000502:physiology* / Q000648:ultrastructure; D009842:Oligopeptides; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001685:Biological Factors; D017630:Connexins; D009842:Oligopeptides; C067410:endothelium-dependent hyperpolarization factor; C455880:gap 27 peptide; D000109:Acetylcholine