Proteolytic activities in hypertensive cardiomyopathy of rats.
Two-kidney, one clip Goldblatt hypertension of 2, 4 and 8 weeks duration was induced in 100-g male Wistar-Kyoto rats. Nucleic acid content was determined in the isolated cardiac muscle cells from the left ventricle. The profile for several major proteolytic activities in either isolated cardiac muscle cells or left ventricle preparations was also studied, using [3H]acetyl-casein as substrate. From the soluble fraction of the tissue or cell preparation, a pH 6 proteolytic activity, two forms of calcium-activated protease as well as cathepsin D were identifiable by inhibitor assay or DEAE-cellulose chromatography. From the myofibrillar fraction of the same preparation, two kinds of proteolytic activity were detected at alkaline pH: a phenylmethylsulfonyl fluoride (PMSF) inhibitable activity that was serine protease-like and the other a N-ethylmaleimide (NEM) inhibitable activity that resembled Ca2+-activated protease. At 2 weeks of hypertension, there was a significant increase in the pH 6 proteolytic activity as well as the calcium-activated protease I and the NEM-inhibitable alkaline protease activities, while the other identifiable proteolytic activities remained unchanged. Lysosomal cathepsin D showed a rise in activity only after 8 weeks of hypertension. These results may be related to the development of myocyte necrosis and lysis that occur in this model of hypertensive cardiomyopathy.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D009202:Cardiomyopathies / Q000201:enzymology* / Q000209:etiology; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006977:Hypertension, Renal / Q000150:complications*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010664:Phenylmethylsulfonyl Fluoride; D002403:Cathepsins; D010447:Peptide Hydrolases; D002402:Cathepsin D; D005033:Ethylmaleimide; D002118:Calcium