Related Experiment Videos
Dissociation between regional dysfunction and beta-adrenergic receptor signaling in heart failure
1Veterans Affairs Medical Center-San Diego and Department of Medicine, University of California San Diego, La Jolla, California 92161, USA.
The American Journal of Physiology
|September 24, 1998
Summary
Heart failure reduces beta-adrenergic receptor (beta-AR) signaling systemically, not regionally. This means altered beta-AR signaling in specific heart regions doesn't predict regional wall thickening during heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Left ventricular (LV) pacing-induced heart failure shows preserved interventricular septum (IVS) wall thickening compared to the posterolateral wall (PLW).
- Understanding the link between regional myocardial function and beta-adrenergic receptor (beta-AR) signaling is crucial in heart failure.
Purpose of the Study:
- To investigate the relationship between regional myocardial function and altered beta-adrenergic receptor (beta-AR) signaling in LV pacing-induced heart failure.
- To determine if regional differences in myocardial function correlate with regional beta-AR signaling abnormalities.
Main Methods:
- Studied 15 pigs (6 controls, 9 with LV pacing-induced heart failure for 26 days).
- Assessed heart failure via LV fractional shortening and left atrial pressure.
- Measured regional myocardial function (wall thickening) and beta-AR responsiveness (dobutamine infusion).
- Quantified adenylyl cyclase activity, beta-AR number, beta-AR/Gs coupling, and G protein receptor kinase (GRK) isoforms (GRK2, GRK5).
Main Results:
- Heart failure was confirmed by decreased LV fractional shortening and increased left atrial pressure.
- Despite significant regional differences in basal wall thickening (IVS vs. PLW), beta-AR responsiveness and signaling measurements showed no regional variations.
- Adenylyl cyclase activity, beta-AR number, and beta-AR/Gs coupling were globally reduced in heart failure.
- GRK5 levels were significantly increased in both IVS and PLW in heart failure, without regional differences.
Conclusions:
- Systemic factors, not regional ones, control LV adrenergic signaling in this model of heart failure.
- Regional adrenergic signaling abnormalities do not reliably predict wall thickening in the same myocardial regions.
- The preserved IVS function in LV pacing-induced heart failure is not explained by regional differences in beta-AR signaling.