Adrenergic induction of bimodal myocardial protection: signal transductionand cardiac gene reprogramming

Citation
Xz. Meng et al., Adrenergic induction of bimodal myocardial protection: signal transductionand cardiac gene reprogramming, AM J P-REG, 45(5), 1999, pp. R1525-R1533
Citations number
44
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
ISSN journal
03636119 → ACNP
Volume
45
Issue
5
Year of publication
1999
Pages
R1525 - R1533
Database
ISI
SICI code
0363-6119(199905)45:5<R1525:AIOBMP>2.0.ZU;2-F
Abstract
This study tested the hypothesis that in vivo norepinephrine (NE) treatment induces bimodal cardiac functional protection against ischemia and examine d the roles of alpha(1)-adrenoceptors, protein kinase C (PKC), and cardiac gene expression in cardiac protection. Rats were treated with NE (25 mu g/k g iv). Cardiac functional resistance to ischemia-reperfusion (25/40 min) in jury was examined 30 min and 1, 4, and 24 h after NE treatment with the Lan gendorff technique, and effects of alpha(1)-adrenoceptor antagonism and PKC inhibition on the protection were determined. Northern analysis was perfor med to examine cardiac expression of mRNAs encoding alpha-actin and myosin heavy chain (MHC) isoforms. Immunofluorescent staining was performed to loc alize PKC-beta I in the ventricular myocardium. NE treatment improved posti schemic functional recovery at 30 min, 4 h, and 24 h but not at 1 h. Pretre atment with prazosin or chelerythrine abolished both the early adaptive res ponse at 30 min and the delayed adaptive response at 24 h. NE treatment ind uced intranuclear translocation of PKC-beta I in cardiac myocytes at 10 min and increased skeletal alpha-actin and beta-MHC mRNAs in the myocardium at 4-24 h. These results demonstrate that in vivo NE treatment induces bimoda l myocardial functional adaptation to ischemia in a rat model. alpha(1)-Adr enoceptors and PKC appear to be involved in signal transduction for inducin g both the early and delayed adaptive responses. The delayed adaptive respo nse is associated with the expression of cardiac genes encoding fetal contr actile proteins, and PKC-beta I may transduce the signal for reprogramming of cardiac gene expression.