title: Relative contributions of NO and gap junctional communication to endothelium-dependent relaxations of rabbit resistance arteries vary with vessel size.
abstract: Two synthetic peptide inhibitors of gap junctional communication have been used to compare the contribution of direct cell-cell coupling to acetylcholine-induced relaxations of the rabbit central ear artery (G(0)) and its second branch generation (G(2)). These peptides, designated (43)Gap 26 and (37,43)Gap 27, possess sequence homology with specific domains of the first extracellular loop of connexin 43 (Cx43) and second extracellular loop of Cxs 37 and 43, respectively. Immunohistochemistry confirmed the presence of Cxs 37, 40, and 43 in the vascular endothelium, but of only Cx43 in the media of G(0). At concentrations of 300 microM, (43)Gap 26 and (37,43)Gap 27 each inhibited the maximum response to acetylcholine in G(2) by approximately 50%, but by only approximately 20% in G(0), whereas inhibition of NO synthesis by 300 microM N(G)-nitro-L-arginine methyl ester attenuated maximum relaxations to acetylcholine by approximately 30% in G(2), but by approximately 70% in G(0). Residual endothelium-derived hyperpolanizing factor-type responses in G(0) and G(2) were abolished by (43)Gap 26 and (37,43)Gap 27. In HeLa cells transfected to express a chimeric Cx43-green fluorescent protein that forms functional gap junctions, the peptides were equally effective inhibitors of Lucifer yellow dye transfer. We conclude that the contribution of gap junctions to endothelium-dependent relaxation is inversely related to vessel size and exhibits an apparently reciprocal relationship with NO-mediated mechanisms of vasorelaxation in the rabbit ear.
authors.affiliation: Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, Wales, United Kingdom.
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Berman
authors.forename: Patricia E M
authors.initials: PE
authors.lastname: Martin
authors.forename: W Howard
authors.initials: WH
authors.lastname: Evans
authors.forename: Tudor M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000502:physiology; D018031:Connexin 43 / Q000096:biosynthesis; D017630:Connexins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D000109:Acetylcholine; D018031:Connexin 43; D017630:Connexins; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D007546:Isoquinolines; D008164:Luminescent Proteins; D009569:Nitric Oxide; D011993:Recombinant Fusion Proteins; D014665:Vasodilator Agents; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C017475:lucifer yellow