Adverse effects of constitutively active alpha(1B)-adrenergic receptors after pressure overload in mouse hearts

• Published in: American journal of physiology. Heart and circulatory physiology 2000-09, Vol.279 (3), p.H1079-H1086
• Main Authors: Wang, B H, Du, X J, Autelitano, D J, Milano, C A, Woodcock, E A
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists - pharmacology; Animals; Aorta, Thoracic - physiology; Aorta, Thoracic - surgery; Atrial Natriuretic Factor - genetics; Atrial Natriuretic Factor - metabolism; Binding, Competitive - drug effects; Binding, Competitive - genetics; Blood Pressure; Cardiac Myosins; Cardiomegaly - genetics; Cardiomegaly - metabolism; Constriction, Pathologic; Down-Regulation - genetics; Heart - physiopathology; Lung - pathology; Mice; Mice, Inbred Strains; Mice, Transgenic; Myocardium - metabolism; Myosin Light Chains - biosynthesis; Organ Size; Pressure; Promoter Regions, Genetic; Radioligand Assay; Receptors, Adrenergic, alpha-1 - genetics; Receptors, Adrenergic, alpha-1 - metabolism; RNA, Messenger - biosynthesis; Thrombosis - pathology
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.2000.279.3.h1079

Cardiac hypertrophy and function were studied 6 wk after constriction of the thoracic aorta (TAC) in transgenic (TG) mice expressing constitutively active mutant alpha(1B)-adrenergic receptors (ARs) in the heart. Hearts from sham-operated TG animals and nontransgenic littermates (WT) were similar in size, but hearts from TAC/TG mice were larger than those from TAC/WT mice, and atrial natriuretic peptide mRNA expression was also higher. Lung weight was markedly increased in TAC/TG animals, and the incidence of left atrial thrombus formation was significantly higher. Ventricular contractility in anesthetized animals, although it was increased in TAC/WT hearts, was unchanged in TAC/TG hearts, implying cardiac decompensation and progression to failure in TG mice. There was no increase in alpha(1A)-AR mRNA expression in TAC/WT hearts, and expression was significantly reduced in TAC/TG hearts. These findings show that cardiac expression of constitutively actively mutant alpha(1B)-ARs is detrimental in terms of hypertrophy and cardiac function after pressure overload and that increased alpha(1A)-AR mRNA expression is not a feature of the hypertrophic response in this murine model.