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Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology

Sexual dimorphism in oxidant status in spontaneously hypertensive rats

¹Vascular Biology Center and ²Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia

Submitted 12 May 2006 ; accepted in final form 13 August 2006

Male spontaneously hypertensive rats (SHR) have a blunted pressure-natriuresis relationship and enhanced oxidative stress compared with female SHR. Furthermore, oxidative stress contributes to abnormal renal Na⁺ handling and renal damage in hypertension. The aim of this study was to determine whether a sex difference exists in renal inner medullary hydrogen peroxide (H₂O₂) levels and/or antioxidant systems in SHR and the influence of sex steroids on these systems. Thirteen-week-old intact and gonadectomized male and female SHR were placed in metabolic cages for 24-h urine collection. Renal inner medullas were isolated for antioxidant activity assays and Western blot analysis or for measurements of H₂O₂ using Amplex Red. Studies verified that male SHR had greater Na⁺ reabsorption compared with female SHR. Male SHR had enhanced urinary excretion of H₂O₂ compared with female SHR. Gonadectomy decreased H₂O₂ excretion in males and increased H₂O₂ excretion in females, suggesting that testosterone stimulates total body oxidative stress and estrogen suppresses levels of total body oxidative stress. There was not a sex difference in inner medullary H₂O₂ levels. Male SHR had a testosterone-dependent increase in inner medullary SOD activity, and both intact and gonadectomized males had high levels of inner medullary catalase activity compared with females. The results of this study showed that there was a sexual dimorphism in Na⁺ handling and oxidant status. We hypothesize that there is a testosterone-sensitive increase in whole body reactive oxygen species production that results in a compensatory increase in the inner medullary antioxidant capability possibly to normalize Na⁺ handling.

oxidative stress; antioxidants; free radicals; kidney

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