title: Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats.
abstract: Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) and associated cardiovascular disease. To induce kidney damage in male and female Wistar rats (n = 12/group), a 0.25% adenine diet for 16 wk was used. Kidney function (blood urea nitrogen, plasma creatinine, proteinuria) and structure (glomerular damage, tubulointerstitial atrophy, fibrosis, inflammation); cardiovascular function (blood pressure, ventricular stiffness, vascular responses, echocardiography) and structure (cardiac fibrosis); plasma testosterone and estrogen concentrations; and protein expression for oxidative stress [heme oxygenase-1, inflammation (TNF-α), fibrosis (transforming growth factor-β), ERK1/2, and estrogen receptor-α (ER-α)] were compared in males and females. Adenine-fed females had less decline in kidney function than adenine-fed males, although kidney atrophy, inflammation, and fibrosis were similar. Plasma estrogen concentrations increased and plasma testosterone concentrations decreased in adenine-fed males, with smaller changes in females. CKD-associated molecular changes in kidneys were more pronounced in males than females except for expression of ER-α in the kidney, which was completely suppressed in adenine-fed males but unchanged in adenine-fed females. Both genders showed increased blood pressure, ventricular stiffness, and cardiac fibrosis with the adenine diet. Cardiovascular changes with adenine were similar in males and females, except males developed concentric, and females eccentric cardiac hypertrophy. In hearts from adenine-fed male and female rats, expression of ER-α and activation of the ERK1/2 pathway were increased, in part explaining changes in cardiac hypertrophy. In summary, adenine-induced kidney damage may be increased in males due to the suppression of ER-α.
authors.affiliation: School of Biomedical Science, The University of Queensland, Brisbane, Australia; Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia; and.
authors.forename: Vishal
authors.initials: V
authors.lastname: Diwan
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia; and.
authors.forename: David
authors.initials: D
authors.lastname: Small
authors.affiliation: School of Health, Nursing and Midwifery, The University of Southern Queensland, Toowoomba, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Kauter
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia; and.
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
authors.affiliation: School of Health, Nursing and Midwifery, The University of Southern Queensland, Toowoomba, Australia Lindsay.Brown@usq.edu.au.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
mesh_terms: D000225:Adenine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging; D004967:Estrogens / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism; D014463:Ultrasonography; D014563:Urodynamics / Q000502:physiology
chemical_list: D004967:Estrogens; D013739:Testosterone; D000225:Adenine
keywords: ERK1/2; cardiovascular disease; chronic kidney disease; estrogen receptor-α; inflammation