Developmental regulation of ace gene expression by endogenous kinins and angiotensin ii. Yosipiv, Igor V., and Samir S. El-Dahr. Department of Pediatrics, Division of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, Louisiana 70112
APStracts 2:0025F, 1995.
ACE (kininase II), a key regulator of kinins and angiotensin (ANG) II generation, is developmentally regulated and its expression is induced at a specific time point (day 15) of postnatal kidney development. The present study tested the hypothesis that endogenous kinins and ANG II regulate the developmental expression of the renal ACE gene. In the first protocol, newborn rats received the kallikrein inhibitor, aprotinin (100,000 KIU/kg/d s.c.), or the kinin B2 -receptor antagonist, HOE 140 (600 Ng/kg/d s.c.), or 0.9% saline, from birth until postnatal days 5, 15 or 20. Aprotinin prevented the postnatal rise in renal kallikrein activity without affecting blood pressure in either developing or adult rats. Chronic kallikrein blockade significantly attenuated the postnatal induction of both serum ACE activity (-11% vs. controls) and kidney ACE activity and mRNA (-50% vs. controls). In addition, aprotinin attenuated the postnatal rise of ACE activity in the developing lungs. Kidney renin mRNA and ANG II contents were not altered by aprotinin. HOE 140 also attenuated the postnatal rise in kidney ACE mRNA (-25%) and activity (-40%) without affecting blood pressure. Infusion of aprotinin or HOE 140 via osmotic minipumps for 7 days in adult rats was not associated with any changes in renal or pulmonary ACE. In the second protocol, newborn and adult rats received the ANG II type 1 receptor (AT1) antagonist, losartan (10 mg/kg/d, s.c.), or saline for 5 days. AT1 blockade increased ACE mRNA and enzymatic activity (2.3-fold) and renin mRNA levels (12-fold) in both newborn and adult kidneys. AT1 blockade had no effects on ACE activity in the lung or heart. Based on these data, we conclude that renal kallikrein and ACE are co -regulated during development. Endogenous kinins and ANG II, acting via their respective receptors, function as positive and negative regulators, respectively, of renal ACE gene expression and activity during development. 

Received 15 August 1994; accepted in final form 17 February 1995.
APS Manuscript Number F288-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  1 March 1995.