title: Gap junction-dependent and -independent EDHF-type relaxations may involve smooth muscle cAMP accumulation.
abstract: We have compared the mechanisms that contribute to endothelium-derived hyperpolarizing factor (EDHF)-type responses induced by ACh and the Ca(2+) ionophore A-23187 in the rabbit iliac artery. Relaxations to both agents were associated with ~1.5-fold elevations in smooth muscle cAMP levels and were attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA) and potentiated by the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Mechanical responses were inhibited by coadministration of the Ca(2+)-activated K(+) channel blockers apamin and charybdotoxin, both in the absence and presence of IBMX, but were unaffected by blockade of ATP-sensitive K(+) channels with the sulphonylurea glibenclamide. Relaxations and elevations in cAMP evoked by ACh were abolished by 18alpha-glycyrrhetinic acid, which disrupts gap junction plaques, whereas the corresponding responses to A-23187 were unaffected by this agent. Consistently, in "sandwich" bioassay experiments, A-23187, but not ACh, elicited extracellular release of a factor that evoked relaxations that were inhibited by DDA and potentiated by IBMX. These findings provide evidence that EDHF-type relaxations of rabbit iliac arteries evoked by ACh and A-23187 depend on cAMP accumulation in smooth muscle, but involve signaling via myoendothelial gap junctions and the extracellular space, respectively.
authors.affiliation: Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chaytor
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Taylor
authors.forename: Tudor M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D007083:Iliac Artery / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011817:Rabbits
chemical_list: D001685:Biological Factors; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D000001:Calcimycin; D000242:Cyclic AMP; D000109:Acetylcholine; D005905:Glyburide; D015056:1-Methyl-3-isobutylxanthine; D019331:NG-Nitroarginine Methyl Ester