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1 Physiology, School of Medicine, University of Murcia, Murcia, Murcia, Spain
2 Physiology, School of Medicine, University of Murcia, Murcia, Murcia, Spain; Murcia, Murcia, Spain
3 physiology, University of Murcia, Murcia, Spain
* To whom correspondence should be addressed. E-mail: salaza{at}um.es.
This study was designed to test the hypothesis that blockade of angiotensin II effects during renal development accelerates the ageing-related changes in renal hemodynamics and proteinuria, and that these changes are gender-dependent. It has also been examined whether the deterioration of urinary concentrating ability elicited by angiotensin II blockade is gender and/or ageing dependent. Newborn SD rats were treated with vehicle or an AT1 angiotensin II receptor antagonist (ARA) during the first 14 postnatal days. Blood pressure, glomerular filtration rate (GFR), proteinuria and urinary concentrating ability in response to dehydration were examined in conscious rats at 3 and 11 months 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 months of age. GFR only decreased (p<0.05) in 11 months old male ARA-treated rats (0.59 ± 0.07 vs 0.80 ± 0.07 ml/min/g in control group). At 3 months of age, proteinuria increased in males (107%) but not in females ARA-treated rats. However, at 11 months of age, proteinuria increased in both sexes but the increment was greater (p<0.05) in males (244%) than in females (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 ageing. Therefore, we conclude that blockade of angiotensin II effects during renal development elicits an important deterioration of cortical and medullary function that is gender and ageing-dependent.
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