β -Adrenergic Cardiac Hypertrophy is Mediated Primarily by the β1-Subtype in the Rat Heart

Myocardial β -adrenergic receptors (β -ARs) consist ofβ1 - and β2-subtypes, which mediate distinct signaling mechanisms. We examined whichβ -AR subtype mediates cardiac hypertrophy. The β2-subtype is predominant in neonatal rat cardiac myocytes (β1, 36%vβ2, 64%), while theβ1 -subtype predominates in the adult rat heart (59%v 41%). Stimulation of cultured cardiac myocytes in vitro with isoproterenol (ISO), an agonist for β1- andβ2 -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 aβ1 -AR antagonist, betaxolol, but not by a β2-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 β -AR stimulated hypertrophy is mediated by theβ1 -subtype and by a pertussis toxin-insensitive mechanism