Hypertension, Vol 5, 706-711, Copyright © 1983 by American Heart Association
K Shimoda, TC Lee and MH Maxwell
The effect of the potassium-sparing diuretic, amiloride, was studied in
conscious rabbits bearing chronic indwelling cannulas to assess whether its
reported in vitro kallikrein-inhibiting activity may produce a suppressive
effect on furosemide-induced renin secretion similar to that previously
demonstrated with another kallikrein inhibitor, aprotinin. Furosemide
elicited a rapid and persistent rise in plasma renin activity (PRA), but
pretreatment of the same rabbits with a 15- minute intravenous infusion of
amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before
furosemide, completely prevented this rise. Amiloride also prevented
furosemide-induced kaliuresis without an attenuation of the diuretic or
natriuretic response and did not alter plasma potassium concentration in
the absence of any change in external potassium balance, indicating that
suppression of the PRA response is due neither to prevention of
extracellular fluid volume contraction nor to the known suppressive effect
of hyperkalemia. Mean arterial pressure tended to fall slightly but not
significantly with or without amiloride pretreatment. On the basis of these
findings and those of our antecedent study with aprotinin, we conclude that
the striking similarity between the suppressive effects of two dissimilar
inhibitors of kallikrein on pharmacologically evoked renin secretion is
consistent with the hypothesis that renal kallikrein participates in the
mechanism of renin secretion in vivo.
ARTICLES
Inhibition of furosemide-induced increases in plasma renin activity by amiloride