Myocardial enzymatic activity of renin and cathepsin D before and after bilateral nephrectomy.
A local renin-angiotensin system is present within the myocardium and can play a role in the initiation and maintenance of cardiac hypertrophy. The source of myocardial renin maybe direct cardiac renin gene expression, or plasma renin of renal origin. A primary indication that myocardial renin is derived from plasma renin of renal origin was from work showing that cardiac renin activity was no longer detected 30 hours after bilateral nephrectomy (BNX). However, more recent studies have been able to detect myocardial renin after BNX. We measured normal rat cardiac renin before and after 48-hour BNX using a myocardial renin assay with improved sensitivity. The myocardial renin assay was also used to assess normal rat cardiac myocyte renin levels. Since cardiac tissue contains cathepsin D, a lysosomal enzyme capable of renin-like activity, a rat cathepsin D assay was also developed to assess cathepsin D contribution to renin-like activity. Several artifacts were shown to contribute to myocardial renin-like enzymatic activity levels after BNX, including initial plasma renin stimulation during BNX surgery, assay pH, and cardiac cathepsin D activity. Myocardial renin concentration after 48-BNX was found to be only approximately 1% of normal control levels, and renin concentration in normal cardiac myocytes was only 2-fold greater than assay blanks. Both results were probably overestimated due to cathepsin D contamination. In conclusion, no evidence was found for myocardial renin synthesis in the normal adult rat heart, and myocardial renin decays to near zero levels after 48-hour BNX.
Katz
S A
SA
Department of Physiology, University of Minnesota School of Medicine, Minneapolis 55455, USA. katzx001@umn.edu
Opsahl
J A
JA
Forbis
L M
LM
D000758:Anesthesia; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D002402:Cathepsin D / Q000032:analysis / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009392:Nephrectomy; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
D000809:Angiotensins; D010436:Pepstatins; D011480:Protease Inhibitors; D012083:Renin; D002402:Cathepsin D; C031375:pepstatin