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.