Urinary kallikrein in rats bred for their susceptibility and resistance to the hypertensive effect of salt. A new radioimmunoassay for its direct determination.

Abstract

Urinary kallikrein was measured in rats bred to be susceptible (S) or resistant (R) to the hypertensive effect of salt. To determine kallikrein, three different methods were used: (1) a new direct radioimmunoassay (RIA) for the enzymic protein: (2) a method based on the capability of kallikrein, when incubated with kininogen, to generate kinins which were then measured by RIA (kininogenase activity); and (3) a method based on the capability of kallikrein to break the ester bond of p-tosyl-L-arginine methyl ester (HCl (TAMe). A significant correlation ( r = 0.90) was found between the direct RIA and the kininogenase method. It was found that urinary kallikrein was significantly decreased in the S as compared to the R rats by the use of these three methods. Urinary kallikrein in the S rats was much lower when measured by the kininogenase method than by direct RIA or esterolytic assay. This difference could be due to excretion of pre-kallikrein and/or kallikrein bound to an inhibitor (inactive kallikrein). It is suggested that the decrease of urinary kallikrein excretion (active and inactive) in the S rats could be a consequence of a genetic defect that may affect the development of hypertension perhaps through the alteration of sodium and water excretion by the kidney.