Urinary Kallikrein and Urinary Prostaglandin E 2 in Genetically Hypertensive Mice

Abstract

Summary

We have evaluated urinary kallikrein activity and urinary prostaglandin E₂ (PGE₂) immunoreactivity in Schlager high blood pressure (HBP) and low blood pressure (LBP) mice. Urinary kallikrein activity was measured by a colorimetric method employing α-N-p-tosyl-L-arginine methyl ester HCl (TAME) as substrate. It was shown that urinary TAME esterase activity in HBP and LBP mice was probably due to a single enzyme and that this enzyme appeared to be urinary kallikrein. Urinary PGE₂ immunoreactivity was determined by a specific radioimmunoassay. Urinary kallikrein activity was significantly elevated and urinary PGE₂ immunoreactivity was significantly reduced in HBP compared to LBP mice. High urinary kallikrein activity in HBP mice resembles situations such as human primary aldosteronism, where hypertension is produced by mineralocorticoid excess. Low urinary PGE₂ levels in HBP mice, however, compares to the situation observed for human essential hypertension. The HBP mouse thus has alterations in physiological parameters believed to reflect renal blood pressure regulating mechanisms. These alterations are unique among genetically hypertensive animal models and appear to be analogous to alterations seen in certain human hypertensive states. One possible explanation for the inverse relationship between urinary kallikrein activity and urinary PGE₂ levels in HBP and LBP mice is that HBP mice could have a physiological block preventing stimulation of renal prostaglandin synthesis by the renal kallikrein-kinin system.

We are indebted to D. W. Sandwisch for his very helpful technical advice and to P. K. Howell for her technical assistance.