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COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging. | LitMetric

AI Article Synopsis

Article Abstract

This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P < 0.05). This reduction in renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P < 0.05) COX2np-treated rats. Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

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http://dx.doi.org/10.1152/ajprenal.00535.2013DOI Listing

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