Effects of losartan on the collagen degradative enzymes in hypertrophic and congestive types of cardiomyopathic hamsters.
The present study was undertaken to determine the effects of AT1 receptor blockade which occurred in response to losartan, on the extracellular matrix (ECM) degradation process in the Bio 14.6 (n = 12) and Bio 53.58 (n = 12) strains which are referred as models of hypertrophic and dilated cardiomyopathy, respectively. The administration of losartan (30 mg/kg/day) in hamsters from 10-20 weeks of age reduced the accumulation of the left ventricular collagen matrix in both of the Bio 14.6 and the Bio 53.58 strains. According to the RT-PCR, the levels of mRNA for matrix metalloproteinase (MMP) and the tissue inhibitor of MMP (TIMP) were examined. MMP-1, -2, -3, and -9 were more enhanced in both myopathic strains than in the control F1beta, strains. With losartan, the levels of MMP-1, -2, -9, TIMP-1 and -2 decreased in the both strains but those for MMP-3 did not in Bio 14.6 strains. TIMP-3 and -4 mRNA levels did not change in any of the experimental hamsters, whether treated or untreated with losartan. The Western blots also showed similar observations in the both strains as seen in mRNA expressions although MMP-2 in the Bio 53.58 strains did not differ between treated and untreated with losartan. Although losartan has an inhibitory effect on collagen accumulation in the development of cardiomyopathy, MMPs (-1, -2, -9) and TIMPs (-1, -2) seem to be susceptible to responding to losartan in Bio cardiomyopathic hamsters.
Masutomo
K
K
Department of Molecular and Cellular Biology Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Makino
N
N
Fushiki
M S
MS
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases; D019808:Losartan