AJP - Renal Physiology, Vol 261, Issue 6 975-F981, Copyright © 1991 by American Physiological Society
Differing renal effects of activated and nonactivated isoelectric peaks of human prorenin in rats
J. K. McKenzie, D. R. Jones, I. M. McKenzie and D. D. Smyth
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Isoelectric species of renin are physically heterogeneous. Recent evidence
suggests that they may differ functionally, with some species producing
natriuresis and diuresis, whereas others have no effect. A physiological
function of secreted prorenin has not been documented in any species. The
present study was designed to confirm and describe for the first time the
renal effects of certain isoelectric species of prorenin. Anesthetized
Sprague-Dawley rats were injected (0.1 ml) with trypsin-activated or
nonactivated prorenin obtained from human ovarian follicular fluid. The
dose chosen was calculated as sufficient to produce 2,300 ng angiotensin
I.h-1.100 g rat body wt-1 in the presence of excess sheep substrate. Blood
pressure, creatinine clearance, urine flow rate, and urine sodium,
potassium, and osmolar excretion were measured. Activated prorenin from
isoelectric peaks at isoelectric points (pI) 5.1, 5.2, 5.4, and 5.6
produced marked increases in urine volume (sixfold) and sodium excretion
(7- to 10-fold) compared with the group receiving the vehicle (1% albumin
in 0.9% saline). Activated prorenin from peaks at pI 4.9 and 5.8 produced
no significant increase over the vehicle-only experiments. Captopril
pretreatment (1 mg/kg iv) completely blocked the effects of peaks at pI 5.4
and 5.6. Interestingly, injection of nonactivated prorenin from peaks at pI
5.4 and 5.6 produced effects similar to the injection of activated prorenin
from these peaks. Similarly, this effect was blocked by pretreatment with
captopril. In summary, only certain isoelectric peaks of human prorenin
whether activated, to active renin, or nonactivated produced a marked
natriuresis and diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
