Total and kallikrein arginine esterase activities in the urine of salt-hypertensive susceptible and resistant rats.

Abstract

Urinary enzymes that hydrolyze the artificial substrate alpha-N-p-tosyl-L-arginine methyl ester (TAME) were studied in Dahl salt-sensitive (S) and salt-resistant (R) rats. Total urinary TAME esterase activity (kallikrein and non-kallikrein) showed a marked increase with dialysis against water, but only in hypertensive S rats with proteinuria. This phenomenon suggests the presence of dialyzable TAME esterase inhibitor(s) in urine following renal damage, but these data do not define what urinary esterases might be affected. Partially purified urinary kallikrein exhibited a ratio of kininogenase to esterase activity which was equal for S and R rats. Thus, the marked discrepancy between kininogenase and esterase activities reported by Carretero et al. with S and R whole urine is not a function of the S and R kallikrein molecules but is probably related to interfering substances in the whole urine. Urinary kallikrein excretion was measured on individual rat samples by TAME esterase activity following dialysis and separation from non-kallikrein TAME esterase(s) using DEAE-Sephadex minicolumns. S rats had lower urinary kallikrein excretion that R when the S rats were hypertensive and showed marked proteinuria. Young S and R rats raised on low salt showed similar blood pressures and similar kallikrein excretion. High salt (8% NaCl) diet decreased kallikrein excretion in both S and R, but the decrease was greater in the S rats which became hypertensive and had increased urine protein excretion. These data suggest that the lower urinary kallikrein excretion in S rats relative to R rats is probably a consequence of hypertension and renal damage rather than a primary cause of hypertension.