Cyclic AMP mediates EDHF-type relaxations of rabbit jugular vein.
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.
Griffith
T M
TM
Cardiovascular Sciences Research Group, University of Wales College of Medicine, Cardiff, CF4 4XN, United Kingdom. griffith@cardiff.ac.uk
Taylor
H J
HJ
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
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