β-Adrenergic cardiac hypertrophy is mediated primarily by the β1-subtype in the rat heart

Myocardial P-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 nconatal rat cardiac myocytes (beta (1), 36% v beta (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. (C) 2001 Academic Press.