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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.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2005 Jan; Vol. 144 (1), pp. 71-9. - Publication Year :
- 2005
-
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.
- Subjects :
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology
8-Bromo Cyclic Adenosine Monophosphate pharmacology
Adenine pharmacology
Adenylyl Cyclase Inhibitors
Animals
Carbazoles pharmacology
Coronary Vessels metabolism
Coronary Vessels physiology
Cyclic AMP antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors
Cyclic GMP antagonists & inhibitors
Cyclic GMP pharmacology
Cyclic GMP-Dependent Protein Kinases antagonists & inhibitors
Drug Interactions
Indoles pharmacology
Isometric Contraction physiology
Isoproterenol pharmacology
Swine
Thionucleotides pharmacology
Time Factors
8-Bromo Cyclic Adenosine Monophosphate analogs & derivatives
Adenine analogs & derivatives
Coronary Vessels drug effects
Cyclic AMP metabolism
Cyclic GMP analogs & derivatives
Cyclic GMP-Dependent Protein Kinases metabolism
Estradiol pharmacology
Isometric Contraction drug effects
Muscle, Smooth, Vascular drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 144
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15644870
- Full Text :
- https://doi.org/10.1038/sj.bjp.0706018