TY - JOUR
T1 - COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging
AU - Reverte, Virginia
AU - Tapia, Antonio
AU - Loria, Analia
AU - Salazar, Francisco
AU - Llinas, M. Teresa
AU - Salazar, F. Javier
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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 COX2nptreated 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.
AB - 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 COX2nptreated 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.
KW - COX2
KW - Fetal programming
KW - Hypertension
KW - Renal function
KW - Renal reserve
KW - Sex-and aging-dependent changes
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U2 - 10.1152/ajprenal.00535.2013
DO - 10.1152/ajprenal.00535.2013
M3 - Article
C2 - 24338820
AN - SCOPUS:84899147371
SN - 1931-857X
VL - 306
SP - F534-F541
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 5
ER -