Prevention of cardiac hypertrophy in experimental chronic renal failure by long-term ACE inhibitor administration: potential role of lysosomal proteinases.
The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinases of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin converting enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/body weight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremic state may be involved in the development of cardiac hypertrophy.
Suzuki
H
H
Department of Internal Medicine, University of Würzburg, Germany.
Schaefer
L
L
Ling
H
H
Schaefer
R M
RM
Dämmrich
J
J
Teschner
M
M
Heidland
A
A
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004656:Enalapril / Q000627:therapeutic use*; D010450:Endopeptidases; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D014700:Verapamil / Q000627:therapeutic use*
D004656:Enalapril; D014700:Verapamil; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat