Evaluation of protein and peptide hydrolases in DOCA-salt hypertensive rat treated with chlorthalidone.

We have reported that chlorthalidone (Chlor) prevents the development of heart hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The present study was carried out to determine whether Chlor (8 mg/day per animal, added to the food, for 20 days) affects kidney and heart hypertrophy in DOCA-salt (8 mg/kg, sc, twice a week) rats by causing alterations in protein and peptide hydrolysis. Heart (left ventricle) and kidney enzyme activities were measured in tissue homogenates from normal-control, salt-control, DOCA-salt and DOCA-salt-Chlor male Wistar rats (N = 6 for each group), using azocasein as the substrate for proteolytic enzymes and specific peptides for prolylendopeptidase (PEP) and multicatalytic proteinase (MCP). The tissue weight/body weight ratio increased in parallel to elevation of blood pressure. The left ventricular muscle hypertrophy (26%, P < 0.05) present in the DOCA-salt hypertensive group was completely prevented by simultaneous Chlor treatment. Chlor treatment did not change the kidney hypertrophy (+79%, P < 0.;05) observed in the salt-control (+57%, P < 0.05) and DOCA-salt (+74%, P < 0.05) groups. The hydrolysis of peptides by PEP and MCP was similar in the normal and salt-control groups. The heart PEP activity was 24% higher (P < 0.01) in DOCA-salt rats, whereas MCP activity was not different when compared to control groups. DOCA-salt treatment increased MCP activity in the kidney by 44% while PEP activity did not differ from that of control groups. The hydrolysis of proteins by heart enzymes was increased by salt by 47%. Chlor treatment restored the reduction in protein hydrolysis induced by DOCA-salt (a 21% decrease, P < 0.05) to a level similar to that of the normal-control group. Similarly, Chlor coadministration prevented the 30% reduction in renal proteolytic activity elicited by DOCA-salt treatment. Although Chlor treatment prevented the DOCA-salt-induced reduction in protein hydrolysis, this response did not interfere with kidney hypertrophy. The mechanism by which hypertension produces hypertrophy is unclear, but our results suggest that this structural modification is not related to the activities of some peptidases, e.g. protein and peptide hydrolases.