Developmental patterns of blood pressure and urinary protein, kallikrein, and prostaglandin E2 in Dahl salt-hypertension-susceptible rats.

S and R female rats were raised on a 1% NaCl diet, and excretion rates of urinary protein, kallikrein esterase activity, and PGE2 were measured (1) at 1 1/2 months of age, when both S and R rats were normotensive, (2) at 3 months of age, when S rats were mildly hypertensive and R controls remained normotensive, and (3) at 6 months of age, when S rats were markedly hypertensive relative to the still normotensive R rats. Urinary protein excretion rate in S compared to R rats was slightly elevated at 1 1/2 months of age and greatly elevated at 3 and 6 months of age. Urinary kallikrein was measured by hydrolysis of TAME after separation of kallikrein from nonkallikrein TAME esterases on DEAE-Sephadex minicolumns. Kallikrein TAME esterase activity was the same in 1 1/2-month-old S and R rats but became reduced in S relative to R rats at 3 and 6 months of age, concomitant with the development of hypertension and marked proteinuria. Urinary PGE2 was decreased in S rats as compared to R rats at all ages, and therefore the strain difference in urinary PGE2 preceded the development of strain differences in blood pressure and urinary kallikrein activity. We conclude that (1) reduced excretion of urinary kallikrein TAME esterase activity in S rats is probably secondary to hypertension and severe proteinuria and (2) decreased urinary PGE2 excretion in prehypertensive S rats is compatible with, but does not prove, the presence of a primary defect in intrarenal PGE2 production that could be involved in initiating hypertension.