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
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.