title: Cyclic AMP mediates EDHF-type relaxations of rabbit jugular vein.
abstract: Isolated rings of rabbit jugular vein have been used to test the hypothesis that formation of cAMP within the endothelial cell contributes to relaxations that are attributable to the endothelium-derived hyperpolarizing factor, EDHF. Relaxations induced by acetylcholine under conditions of combined NO synthase and cyclooxygenase blockade were almost abolished by inhibition of adenylate cyclase with the selective P-site agonist 2', 3'-dideoxyadenosine (2',3'-DDA). They were similarly attenuated by the gap junction inhibitors 18alpha-glycyrrhetinic acid (18alpha-GA) and Gap 27 peptide which interrupt direct endothelium-smooth muscle communication without themselves affecting smooth muscle tone. By contrast, stimulation of adenylate cyclase with forskolin promoted gap junction-dependent relaxations, with concentration-relaxation curves to this agent exhibiting an equivalent rightward shift in the presence of 18alpha-GA and following endothelial denudation. The findings suggest that cAMP may cross from the endothelium to smooth muscle via gap junction channels and/or enhance the endothelial hyperpolarization normally associated with agonist stimulation. Both mechanisms may contribute to EDHF/gap junction-dependent relaxations.
authors.affiliation: Cardiovascular Sciences Research Group, University of Wales College of Medicine, Cardiff, CF4 4XN, United Kingdom. griffith@cardiff.ac.uk
authors.forename: T M
authors.initials: TM
authors.lastname: Griffith
authors.forename: H J
authors.initials: HJ
authors.lastname: Taylor
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C119129:18alpha-glycyrrhetinic acid; D005576:Colforsin; D000242:Cyclic AMP; D000109:Acetylcholine; D006034:Glycyrrhetinic Acid; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin