Angiotensinase C mRNA and Protein Downregulations Are Involved in Ethanol-Deteriorated Left Ventricular Systolic Dysfunction in Spontaneously Hypertensive Rats.
The influences of angiotensinase C on ethanol-induced left ventricular (LV) systolic function were assessed in spontaneously hypertensive rats (SHRs). SHRs were fed by a liquid diet with or without ethanol for 49 days. The normotensive Wistar Kyoto rats (WKY) were fed by the liquid diet without ethanol and used as control. We evaluated LV systolic function, angiotensinase C mRNA and protein expressions, activation of the renin-angiotensin system (RAS), and the gene expressions of LV collagen (Col) III a1 and matrix metalloproteinases- (MMP-) 9. Compared to the WKY, LV systolic dysfunction (expressed by decreased fractional shortening and ejection fraction) was observed in the SHRs before ethanol treatment and further deteriorated by ethanol treatment. In the ethanol-treated SHRs, the following were observed: downregulations of angiotensinase C mRNA and protein, increased RAS activity with low collagen production as evidenced by angiotensin II and angiotensin type 1 receptor (AT1R) protein upregulation, AT1aR mRNA downregulation, and an MMP-9 mRNA expression upregulation trend with the downregulation of Col III a1 mRNA expression in LV. We conclude that chronic ethanol regimen is sufficient to promote the enhanced RAS activity-induced decrease in the production of cardiac collagen via downregulated angiotensinase C, leading to the further deterioration of LV systolic dysfunction in SHRs.
Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Jinyao
J
Liu
Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Ayako
A
Hakucho
Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Tatsuya
T
Fujimiya
D000818:Animals; D062186:Arterial Pressure; D001794:Blood Pressure; D002268:Carboxypeptidases / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000737:chemistry*; D005786:Gene Expression Regulation; D006339:Heart Rate; D006352:Heart Ventricles; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D013599:Systole / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000378:metabolism*
D024061:Collagen Type III; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000431:Ethanol; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat