AJP - Renal Physiology, Vol 245, Issue 2 198-F203, Copyright © 1983 by American Physiological Society
Effect of pH and amiloride on the intrarenal formation of kinins
A. G. Scicli, M. A. Diaz and O. A. Carretero
Changes in urinary kallikrein excretion are assumed to reflect changes in
intrarenal formation of kinins. Yet factors that alter the enzymatic
activity of renal kallikrein and kininases may alter the concentration of
kinins in the nephron independent of amount of kallikrein excreted. In
anesthetized rats, we measured excretion of urinary kallikrein
(kininogenase activity) and kinin excretion during altered urinary pH and
after amiloride, which reportedly inhibits urinary kallikrein. In rats fed
a low sodium diet, urine was acidified by intravenous 0.28 M sodium
sulfate. This decreased urinary pH from 6.1 +/- 0.09 to 5.3 +/- 0.17 and
urinary kinin excretion from 28.0 +/- 9.0 to 10.5 +/- 5.0 pg/min. Urinary
kallikrein excretion doubled from 43.0 +/- 5.0 to 82.5 +/- 13.5 ng/min. The
optimum pH of kallikrein is congruent to 8.5, so the decreased excretion of
urinary kinins is probably secondary to decreased kininogenase activity at
lower urinary pH. Amiloride decreased urinary kinins from 35.5 +/- 7.3 to
18.2 +/- 2.5 pg/min and kallikrein from 18.7 +/- 4.9 to 9.3 +/- 1.8 ng/min,
while urinary pH increased from 6.7 +/- 0.07 to 7.3 +/- 0.07. The depressed
excretion of kallikrein and kinins with amiloride may not have been due to
inhibition of kallikrein, since amiloride (1 mM) did not inhibit the
kininogenase activity of rat urinary kallikrein (congruent to 1.2 nM) on
dog or rat kininogen in vitro. We conclude that changes in urinary
kallikrein may not reflect changes in intrarenal formation of kinins. These
data also indicate that kallikrein excretion increases and kinin formation
decreases when urine is acidified in the distal nephron and that there may
be a link between the kallikrein-kinin system and the renal mechanisms
affected by amiloride.
