Recombinant bovine growth hormone-induced reduction of atrial natriuretic peptide is associated with improved left ventricular contractility and reverse remodeling in cardiomyopathic UM-X7.1 hamsters with congestive heart failure.
OBJECTIVE
To assess the effect of short-term treatment with GH on left ventricular contractility and remodeling, after the development of heart failure in cardiomyopathic hamsters (CMH).


METHODS
Two groups of 200-day-old UM-X7.1 CMH received daily subcutaneous injections of recombinant bovine (rb) GH (1mg/kg/day) or 0.9% NaCl for 40 days. Golden Syrian hamsters (GSH) were used as controls. At 240-day-old, the hamsters were randomly subjected to (i) assessment of left ventricular systolic function in a Langendorff perfused mode followed by the determination of the passive diastolic pressure-volume relationship and morphometric measurements; (ii) assessment of left ventricular mRNA expression of genes belonging to the fetal gene program including atrial (ANP) and brain (BNP) natriuretic peptides and cardiac myosin heavy chain isoforms and of the circulating levels of the natriuretic peptides.


RESULTS
Hearts from CMH were hypertrophied and dilated (p<0.05) compared to hearts from GSH, along with a approximately 10-fold increase in the circulating ANP and BNP levels. Left ventricular BNP and ANP mRNAs were elevated by 2- and 3-fold, respectively, compared to GSH. rbGH reduced both ANP mRNA and ANP circulating levels by 34% (p<0.01) but did not significantly modulate BNP levels. This effect was associated with a preserved systolic function and reverse remodeling as assessed by a leftward shift of the passive diastolic pressure-volume relationship indicating reduced ventricular dilatation.


CONCLUSIONS
The data show that a short-term administration of GH in the terminal phase of the disease confers cardioprotection by attenuating systolic dysfunction and by inducing beneficial reverse remodeling.
Mulumba
Mukandila
M
Faculty of Pharmacy, Université de Montréal, Station Centre-Ville, Montréal, Que, Canada.
Céméus
Catia
C
Dumont
Louis
L
du Souich
Patrick
P
Ong
Huy
H
Marleau
Sylvie
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D006224:Cricetinae; D013006:Growth Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000378:metabolism; D045265:Natriuretic Peptides / Q000097:blood / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D045265:Natriuretic Peptides; D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D013006:Growth Hormone; D018995:Myosin Heavy Chains