title: Adverse effects of constitutively active alpha(1B)-adrenergic receptors after pressure overload in mouse hearts.
abstract: 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.
authors.affiliation: Cellular Biochemistry Laboratory, Baker Medical Research Institute, Prahran 3181, Victoria, Australia.
authors.forename: B H
authors.initials: BH
authors.lastname: Wang
authors.forename: X J
authors.initials: XJ
authors.lastname: Du
authors.forename: D J
authors.initials: DJ
authors.lastname: Autelitano
authors.forename: C A
authors.initials: CA
authors.lastname: Milano
authors.forename: E A
authors.initials: EA
authors.lastname: Woodcock
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects / Q000235:genetics; D001794:Blood Pressure; D024722:Cardiac Myosins; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D003251:Constriction, Pathologic; D015536:Down-Regulation / Q000235:genetics; D006321:Heart / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000096:biosynthesis; D009929:Organ Size; D011312:Pressure; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics* / Q000378:metabolism*; D013927:Thrombosis / Q000473:pathology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018994:Myosin Light Chains; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; C107184:myosin light chain 2; D009320:Atrial Natriuretic Factor; D024722:Cardiac Myosins