Adrenergic induction of bimodal myocardial protection: signal transduction and cardiac gene reprogramming

• Published in: The American journal of physiology Vol. 276; no. 5; pp. R1525 - R1533
• Main Authors: Meng, X, Shames, B D, Pulido, E J, Meldrum, D R, Ao, L, Joo, K S, Harken, A H, Banerjee, A
• Format: Journal Article
• Language: English
• Published: United States 01-05-1999
• Subjects: Actins - genetics; Anesthesia; Animals; Gene Expression Regulation, Enzymologic - drug effects; Hemodynamics - physiology; Isoenzymes - metabolism; Male; Myocardial Contraction - physiology; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - physiopathology; Myocardium - chemistry; Myocardium - enzymology; Myosin Heavy Chains - genetics; Norepinephrine - pharmacology; Protein Kinase C - metabolism; Protein Kinase C beta; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1 - genetics; Receptors, Adrenergic, alpha-1 - metabolism; RNA, Messenger - metabolism; Signal Transduction - physiology; Sympathomimetics - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajpregu.1999.276.5.r1525

This study tested the hypothesis that in vivo norepinephrine (NE) treatment induces bimodal cardiac functional protection against ischemia and examined the roles of alpha1-adrenoceptors, protein kinase C (PKC), and cardiac gene expression in cardiac protection. Rats were treated with NE (25 micrograms/kg iv). Cardiac functional resistance to ischemia-reperfusion (25/40 min) injury was examined 30 min and 1, 4, and 24 h after NE treatment with the Langendorff technique, and effects of alpha1-adrenoceptor antagonism and PKC inhibition on the protection were determined. Northern analysis was performed to examine cardiac expression of mRNAs encoding alpha-actin and myosin heavy chain (MHC) isoforms. Immunofluorescent staining was performed to localize PKC-betaI in the ventricular myocardium. NE treatment improved postischemic functional recovery at 30 min, 4 h, and 24 h but not at 1 h. Pretreatment with prazosin or chelerythrine abolished both the early adaptive response at 30 min and the delayed adaptive response at 24 h. NE treatment induced intranuclear translocation of PKC-betaI 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 bimodal myocardial functional adaptation to ischemia in a rat model. alpha1-Adrenoceptors and PKC appear to be involved in signal transduction for inducing both the early and delayed adaptive responses. The delayed adaptive response is associated with the expression of cardiac genes encoding fetal contractile proteins, and PKC-betaI may transduce the signal for reprogramming of cardiac gene expression.