Beta-adrenergic receptor-G protein-adenylyl cyclase signal transduction in the failing heart

Dorothy E. Vatner, Kuniya Asai, Mitsunori Iwase, Yoshihiro Ishikawa, Richard P. Shannon, Charles J. Homcy, Stephen F. Vatner

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The β-adrenergic receptor signal transduction pathway is critical for rapid adjustments to increased cardiovascular demand (e.g., during exercise). In the face of chronic stimulation of this pathway, as occurs in the pathogenesis of heart failure, β-adrenergic receptor stimulation may become maladaptive. Under these conditions, elevation of circulating catecholamines and depletion of cardiac tissue stores of norepinephrine occur in the failing heart, resulting in desensitization. Whether or not stimulation or inhibition of the β-adrenergic receptor signaling pathway is beneficial in heart failure is controversial. One approach to address this question is to specifically overexpress a component of the β-adrenergic receptor signaling pathway in a transgenic mouse heart. We have characterized young and old adult mice with overexpressed cardiac G(sα), which couples the β-adrenergic receptor to adenylyl cyclase. In younger animals, β-adrenergic receptor stimulation results in an augmented heart rate and cardiac contractility. Over the life of the animal, however, a picture of cardiomyopathy develops. The result is a dilated heart with a large amount of fibrosis and myocyte hypertrophy, degeneration atrophy, and apoptosis. Conversely, chronic β- adrenergic receptor blockade prevents the development of cardiomyopathy. These experiments support the point of view that chronic β-adrenergic stimulation during the development of heart failure is deleterious and that protecting the heart with chronic β-adrenergic receptor blockade is salutary, conceptually consistent with results of recent clinical trials examining the effects of β-adrenergic receptor blockers in patients with heart failure.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalAmerican Journal of Cardiology
Volume83
Issue number12 A
DOIs
StatePublished - Jun 17 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Beta-adrenergic receptor-G protein-adenylyl cyclase signal transduction in the failing heart'. Together they form a unique fingerprint.

  • Cite this