Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats

Diwan, Vishal and Small, David and Kauter, Kate and Gobe, Glenda C. and Brown, Lindsay (2014) Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats. American Journal of Physiology: Renal Physiology, 307 (11). F1169-F1178. ISSN 1931-857X

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-(3), 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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2014 the American Physiological Society. Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Health, Engineering and Sciences - School of Health, Nursing and Midwifery
Date Deposited: 08 Feb 2015 23:32
Last Modified: 02 Jun 2015 05:33
Uncontrolled Keywords: cardiovascular disease; chronic kidney disease; ERK1/2; estrogen receptor-α; inflammation
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110312 Nephrology and Urology
06 Biological Sciences > 0606 Physiology > 060603 Animal Physiology - Systems
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920106 Endocrine Organs and Diseases (excl. Diabetes)
Identification Number or DOI: 10.1152/ajprenal.00676.2013
URI: http://eprints.usq.edu.au/id/eprint/26714

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