title: COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.
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.
authors: Dept. of Physiology, School of Medicine, Univ. of Murcia, 30100 Murcia, Spain. salazar@um.es.
authors: Virginia
authors: V
authors: Reverte
authors: Antonio
authors: A
authors: Tapia
authors: Analia
authors: A
authors: Loria
authors: Francisco
authors: F
authors: Salazar
authors: M Teresa
authors: MT
authors: Llinas
authors: F Javier
authors: FJ
authors: Salazar
mesh_terms: D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D000804:Angiotensin II
keywords: COX2; fetal programming; hypertension; renal function; renal reserve; sex- and aging-dependent changes