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Coronary artery stenosis in rats affects beta-adrenergic receptor signaling in myocytes.
- Source :
-
Cardiovascular research [Cardiovasc Res] 1997 Jan; Vol. 33 (1), pp. 98-109. - Publication Year :
- 1997
-
Abstract
- Objective: The purpose of this study was to determine whether the early chronic ischemic cardiomyopathy produced by non-occlusive coronary artery constriction was characterized by alterations in the regulation of beta-adrenoreceptor (beta-AR) signaling.<br />Methods: Coronary artery narrowing was surgically induced in rats and the animals sacrificed at 7 and 14 days. The changes in the biochemical properties of the multiple components of the beta-AR pathway were examined in enzymatically dissociated myocytes.<br />Results: Coronary stenosis, involving an average 55% reduction in luminal diameter, was associated with left ventricular failure and right ventricular dysfunction at both time intervals. A decrease in the quantity of beta-AR was detected at 7 days and preceded the loss of high-affinity binding sites. This regulatory modification was characterized by a reduction in beta 1 and beta 2 receptors and a shift in the isoproterenol dose response curve indicating a functional correlation between the decrease in beta-AR and attenuated inotropic support of the myocardium. The percentage of beta-AR binding agonist with high affinity decreased significantly at 14 days along with a further reduction in the density of beta 1 and beta 2 receptors. Reconstitution studies with cyc S49 lymphoma cells did not detect an impairment of Gs alpha functional activity, but the quantity of Gi alpha was increased at both intervals. Finally, activation of the catalytic unit of adenylyl cyclase by forskolin and GTP was not altered by coronary stenosis, however, basal cyclic AMP in myocytes was depressed at 14 days.<br />Conclusions: Coronary stenosis induces distinct and progressive modifications in the beta-AR signaling cascade which may contribute to the impaired ventricular performance in this model of myocardial ischemia.
- Subjects :
- Adrenergic beta-Agonists pharmacology
Animals
Binding Sites
Binding, Competitive
Cell Membrane metabolism
Cyclic AMP metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
GTP-Binding Proteins metabolism
Isoproterenol pharmacology
Male
Myocardium pathology
Rats
Rats, Sprague-Dawley
Ventricular Pressure
Coronary Disease metabolism
Myocardium metabolism
Receptors, Adrenergic, beta metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-6363
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 9059533
- Full Text :
- https://doi.org/10.1016/s0008-6363(96)00190-3