Published Online
on April 2, 2007

A more recent version of this article appeared on June 1, 2007

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Submitted on January 29, 2007
Revised on February 14, 2007

Sex Differences in the Renal Changes Elicited by Angiotensin II Blockade During the Nephrogenic Period

Fara Saez; M. Teresa Castells; Adelina Zuasti; Francisco Salazar; Virginia Reverte; Analia Loria; and F. Javier Salazar^*

From the Departments of Physiology (F. Saez, F. Salazar, V.R., A.L., F.J.S.) and Cell Biology (M.T.C., A.Z.), School of Medicine, University of Murcia, Murcia, Spain.

^* To whom correspondence should be addressed. E-mail: salazar{at}um.es.

Abstract--The renin-angiotensin system plays an important role in renal development. However, it is unknown whether reduction in angiotensin II effects during the nephrogenic period leads to different renal alterations in males and females during the adult age. The aim of this study was to evaluate whether the role of angiotensin II on renal development is sex dependent and whether there are sex differences in blood pressure, renal hemodynamics, and severity of renal damage during adult life when nephrogenesis is altered by blocking angiotensin II effects. Newborn Sprague-Dawley rats were treated with an angiotensin II type 1 receptor antagonist (L-158.809; 7 mg/kg per day) during the first 2 weeks of life. At 3 months of age, changes in blood pressure, albuminuria, and renal hemodynamics were assessed, and stereological and histopathologic studies were performed. Blood pressure increased (127±0.5 versus 115±0.7 mm Hg in control rats; P<0.05) and nephron number decreased (37%; P<0.05) similarly in treated males and females. However, only males had an elevation in albuminuria (5.92±1.65 versus 0.33±0.09 mg per day in control rats; P<0.05), a fall in glomerular filtration rate (12.6%; P<0.05), and a significant decrease in papillary volume (42%; P<0.05). Mean glomerular volume, glomerulosclerosis, arteriolar hypertrophy, and tubulointerstitial damage in cortex and medulla were also higher (P<0.05) in angiotensin II type 1 receptor antagonist-treated males than in treated females. The results of this study suggest that females seem to be more protected than males to the renal consequences of reducing angiotensin II effects during renal development.

Key words: nephrogenesis • sex • angiotensin II • glomerulosclerosis • fibrosis • renal hemodynamics

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