Beta-adrenergic cardiac hypertrophy is mediated primarily by the beta(1)-subtype in the rat heart.
Myocardial beta-adrenergic receptors (beta -ARs) consist of beta(1)- and beta(2)-subtypes, which mediate distinct signaling mechanisms. We examined which beta-AR subtype mediates cardiac hypertrophy. The beta(2)-subtype is predominant in neonatal rat cardiac myocytes (beta(1), 36%vbeta(2), 64%), while the beta(1)-subtype predominates in the adult rat heart (59%v 41%). Stimulation of cultured cardiac myocytes in vitro with isoproterenol (ISO), an agonist for beta(1)- and beta(2)-ARs, caused hypertrophy of myocytes along with increases in transcription of atrial natriuretic factor (ANF) and actin reorganization. All of these ISO-mediated myocyte responses in vitro were inhibited by a beta(1)-AR antagonist, betaxolol, but not by a beta(2)-AR antagonist, ICI 118551. Pertussis toxin failed to affect ISO-induced increases in total protein/DNA content and ANF transcription in vitro. ISO increased LV weight/body weight and ANF transcription in the adult rat in vivo, which were also inhibited by betaxolol but not by ICI 118551. These results suggest that beta -AR stimulated hypertrophy is mediated by the beta(1)-subtype and by a pertussis toxin-insensitive mechanism
Morisco
C
C
Cardiovascular Research Institute and Department of Medicine, University of Medicine and Dentistry of New Jersey, Hackensack, NJ, USA.
Zebrowski
D C
DC
Vatner
D E
DE
Vatner
S F
SF
Sadoshima
J
J
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D006321:Heart; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000378:metabolism
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D011506:Proteins; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol