Overexpression of α1B-adrenergic receptor induces left ventricular dysfunction in the absence of hypertrophy

Author:

Grupp Ingrid L.1,Lorenz John N.2,Walsh Richard A.3,Boivin Gregory P.4,Rindt Hansjörg5

Affiliation:

1. Departments of Pharmacology and Cell Biophysics,

2. Molecular and Cellular Physiology,

3. Internal Medicine, and

4. Pathology, University of Cincinnati, Cincinnati, Ohio 45267; and

5. Department of Medicine, University of Montreal, and Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8

Abstract

The stimulation of cardiac α1-adrenergic receptors (AR) modulates the heart’s inotropic response and plays a role in the induction of cardiomyocyte hypertrophy. We have analyzed transgenic mouse lines overexpressing a wild-type α1B-AR specifically in the heart. Basal level systolic and diastolic left ventricular (LV) contractile function was depressed both in the anesthetized closed-chest mouse and the perfused working-heart preparation. Intrinsic LV function was further characterized under controlled preload and afterload conditions using the perfusion model. Contractile parameters were restored by chronic treatment with the α-AR antagonist prazosin. In ventricular function curves, the load-dependent force increases (length-tension effects) remained intact, although the transgenic curve was shifted to lower levels. The basal level contractile deficits were paralleled by a decrease in calcium transients in isolated LV cardiomyocytes. LV function comparable to controls was restored by isoproterenol stimulation. The physiological changes occurred in the absence of cardiomyocyte hypertrophy. This transgenic model will be useful for studying the potential role of α1-AR in cardiac contractility and hypertrophy.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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