Propranolol prevents enhanced stress signaling in Gsα cardiomyopathy: Potential mechanism for β-blockade in heart failure

Vijaya Karoor, Stephen Vatner, Gen Takagi, Guiping Yang, Jill Thaisz, Junichi Sadoshima, Dorothy Vatner

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Beta-adrenergic receptor (β-AR) blockade is now widely utilized therapeutically for heart failure, but its cellular mechanism of action is not clear. Mice with cardiac-specific overexpressed Gsα develop cardiomyopathy with age, which can be prevented by β-AR blockade, making this model potentially useful for addressing this question. Our hypothesis was that distal mechanisms in β-AR signaling, i.e. mitogen-activated protein kinases, were a potential mechanism. At 6-9 months, when cardiomyopathy began to develop in Gsα mice, there were significant increases in phospho-kinase levels of p38 MAP kinase (p38 MAPK), and p70S6K compared to wild type. In contrast, phospho-kinase levels of ERK and Akt were increased at 9-10 months, but phospho-kinase levels of c-Jun N-terminal kinase (JNK) increased only at 15-20 months (when cardiomyopathy was fully manifest). Treatment of 9-10 months old Gsα mice with propranolol for 5 weeks reverted the phospho-kinase levels of these kinases known to be involved in the growth and death of cardiac myocytes. Another novel observation of this study was that there were also decreases in total protein levels of p38 MAPK, p70 S6K, JNK, and Akt following β-AR blockade. Thus, chronically enhanced β-AR signaling elicits a differential pattern of altered mitogen-activated protein kinases, which was reversed with β-AR blockade, raising the possibility that the beneficial effects of β-AR blockade therapy in heart failure may be due in part to the inhibition of these pathways.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Issue number2
StatePublished - Jan 1 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Propranolol prevents enhanced stress signaling in Gsα cardiomyopathy: Potential mechanism for β-blockade in heart failure'. Together they form a unique fingerprint.

Cite this