Prokallikrein and kallikrein inhibitors in human urine

Abstract

Kallikrein activity (KA) and kallikrein inhibitors (KI) were evaluated in urine from normal subjects and essential hypertensives. Kallikrein inhibitors were almost completely removed by dialysis against water, confirming previous reports of their low molecular size. The negative relationship found between KA and KI in urine samples from 12 normal subjects suggests that KI might play a role in the modulation of KA excreted by the kidney. Heating (85 degrees C for 20 min) partially reduced (-52%) KI, indicating thermostable substances other than peptides as KI. When cations were evaluated as possible KI, by adding different salts to dialysed salt-free urine, only sodium was able to inhibit KA by 20% at a concentration not far from the physiological range. Trypsin added to dialysed urine produced a striking increase in KA without significant changes in Km and pH optimum. These findings, together with the observation that acid dialysis did not increase KA, strongly support the hypothesis that trypsin-activatable kallikrein might be a pro-enzyme. A lower urinary excretion of active kallikrein was found in 48 essential hypertensives when compared with 31 normotensive controls. However, trypsin-activatable kallikrein excretion was similar in the two groups, suggesting that low KA in hypertensives might not reflect a defective conversion of the pro-enzyme into the active form.