Repeated catecholamine surges alter cardiac isomyosin expression but not protein synthesis in the rat heart.
To assess the role of intermittent beta-adrenergic stimulation on alpha-myosin heavy chain expression and cellular hypertrophy, we studied the effect of intermittent dobutamine on myosin heavy chain isoform distribution and protein synthesis in the heterotopic rat heart preparation. This model allows the analysis of a pharmocologic stimulus in isolation from the mechanical load on the myocardium induced by the drug. Intermittent administration of dobutamine resulted in elevated alpha-MHC levels (75 +/- 12%) compared to control (55 +/- 10%; X +/- s.e.; P<0.05) transplanted hearts. This effect was not altered by alpha-receptor blockade with terazosin (72 +/- 8%). Intermittently pacing the transplanted hearts at the same rate as observed with dobutamine alone, also elevated alpha-MHC levels (70 +/- 5%). In contrast, total protein synthesis in the transplanted hearts was not altered with any of the drug or pacing interventions compared to control hearts. These data suggest that intermittent beta-receptor stimulation and/or intermittent increased heart rate contribute to altered patterns of myosin heavy chain expression. However, increases in cardiac mass and protein synthesis are probably mediated by hemodynamic factors rather than catecholamine stimulation.
Geenen
D L
DL
Cardiology Division, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Malhotra
A
A
Scheuer
J
J
Buttrick
P M
PM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D009218:Myosins / Q000096:biosynthesis*; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004280:Dobutamine; C041226:Terazosin; D018995:Myosin Heavy Chains; D009218:Myosins; D011224:Prazosin