title: Acute impairment of contractile responses by 17beta-estradiol is cAMP and protein kinase G dependent in vascular smooth muscle cells of the porcine coronary arteries.
abstract: The aim of the present study was to investigate the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) cascade in the acute impairment of contraction by 17beta-estradiol in porcine coronary arteries, and to elucidate the signaling pathway leading to the activation of this cascade by the hormone. Isometric tension was recorded in isolated rings of porcine coronary arteries. The contraction to U46619 was reduced significantly following 30 min incubation with 1 nM 17beta-estradiol or 1 nM isoproterenol. There was no additive effect when 17beta-estradiol and isoproterenol were administered together. The effect of 17beta-estradiol was mimicked by both the cyclic AMP analogue 8-Br-cAMP and the guanosine 3',5'-cyclic monophosphate (cyclic GMP) analogue 8-Br-cGMP. In rings with and without endothelium, the modulatory effect of 17beta-estradiol was abolished by the adenylyl cyclase inhibitor, SQ 22536, but was unaffected by the guanylyl cyclase inhibitor, ODQ. Both the cAMP antagonist Rp-8-Br-cAMPS and the cGMP antagonist inhibitor Rp-8-Br-cGMPS inhibited the effect of 17beta-estradiol. The effect of 17beta-estradiol was unaffected by the protein kinase A inhibitor, KT5720, but was abolished by the protein kinase G (PKG) inhibitor, KT5823, which also abolished the effect of isoproterenol. These data support our earlier findings that 17beta-estradiol (1 nM) acutely impairs contractile responses of porcine coronary arteries in vitro. This acute effect of 17beta-estradiol involves cAMP in vascular smooth muscles and the activation of PKG.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Level 2, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong SAR, PR China.
authors.forename: Wendy
authors.initials: W
authors.lastname: Keung
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D000067956:Adenylyl Cyclase Inhibitors; D002227:Carbazoles; D007211:Indoles; D013873:Thionucleotides; C073601:KT 5823; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C017759:9-(tetrahydro-2-furyl)-adenine; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D000225:Adenine; D007545:Isoproterenol