title: Sex-dependent hypertension and renal changes in aged rats with altered renal development.
abstract: Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity. Experiments were carried out in rats at 10-11 and 16-17 mo of age treated with vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics were found in both sexes of ARAnp-treated rats, with these changes being greater (P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest age was greater (P < 0.05) in male (74%) than female (32%) ARAnp-treated rats. Sex-dependent deterioration of renal structure was demonstrated in optical and electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced in the macula densa of male but not female ARAnp-treated rats. The present study reports novel findings suggesting that stimuli that induce a decrease of ANG II effects during renal development lead to a progressive increment in BP and renal damage at an old age in both sexes, but these BP and renal changes are greater in males than in females. The renal damage is associated with an increase of COX-2 and NOS1 in the macula densa of males but not females with altered renal development.
authors.affiliation: Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and.
authors.forename: Fara
authors.initials: F
authors.lastname: Saez
authors.affiliation: Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and.
authors.forename: Virginia
authors.initials: V
authors.lastname: Reverte
authors.affiliation: Anatomisches Institut, Charité, Humboldt Universität, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Paliege
authors.affiliation: Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Moreno
authors.affiliation: Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and.
authors.forename: María T
authors.initials: MT
authors.lastname: Llinás
authors.affiliation: Anatomisches Institut, Charité, Humboldt Universität, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.affiliation: Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and salazar@um.es.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Salazar
mesh_terms: D000375:Aging / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; C070967:L 158809; D052248:Nitric Oxide Synthase Type I; D051546:Cyclooxygenase 2
keywords: aging; cyclooxygenase 2; fetal programming; hypertension; neuronal nitric oxide synthase; renal damage; sex differences