Sex and age differences of renal function in rats with reduced ANG II activity during the nephrogenic period

Abstract

This study was designed to test the hypothesis that blockade of angiotensin II effects during renal development accelerates the aging-related changes in renal hemodynamics and proteinuria, and that these changes are sex dependent. It has also been examined whether the deterioration of urinary concentrating ability elicited by angiotensin II blockade is sex and/or aging dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT(1) angiotensin II receptor antagonist (ARA) during the first 14 postnatal days. Blood pressure, glomerular filtration rate, proteinuria, and urinary concentrating ability in response to dehydration were examined in conscious rats at 3 and 11 mo of age. ARA treatment elicited a similar increment in blood pressure in males and females that was greater (P < 0.05) at 11 than at 3 mo of age. Glomerular filtration rate only decreased (P < 0.05) in 11-mo-old male ARA-treated rats (0.59 +/- 0.07 vs. 0.80 +/- 0.07 ml.min(-1).g(-1) in control group). At 3 mo of age, proteinuria increased in male (107%) but not in female ARA-treated rats. However, at 11 mo of age, proteinuria increased in both sexes, but the increment was greater (P < 0.05) in male (244%) than in female (138%) ARA-treated rats. Renal ability to concentrate urine in response to prolonged water dehydration was only reduced in ARA-treated males. The reduction of urinary concentrating ability was accentuated by aging. Therefore, we conclude that blockade of angiotensin II effects during renal development elicits an important deterioration of cortical and medullary function that is sex and aging dependent.