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The hypothesis was tested that differences in oxidative stress play a role in the sex differences in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR).Male and female SHR [and Wistar–Kyoto (WKY) rats in the long-term study] (n = 6–12 per group) received tempol (30 mg/kg per day) or tap water for 6 weeks from 9 to 15 weeks of age or from birth until 15 weeks of age. Blood pressure [mean arterial pressure (MAP)] and kidney tissue F2-isoprostane (IsoP) were measured at 15 weeks of age.In SHR given tempol for 6 weeks, blood pressure and IsoP were reduced in males, but not in females. In SHR given tempol from birth, MAP was higher in SHR than WKY rats (SHR males, 181 ± 2 mmHg; SHR females, 172 ± 3 mmHg; WKY males, 100 ± 2 mmHg; WKY females, 101 ± 2 mmHg, P < 0.01), and tempol reduced MAP by 14% (156 ± 3) and 26% (127 ± 4) in male and female SHR, respectively, but had no effect on WKY rats. IsoP was higher in SHR than WKY rats and higher in male SHR than female SHR (SHR males, 5.18 ± 0.23 ng/mg; SHR females, 3.71 ± 0.19 ng/mg, P < 0.01; WKY males, 1.72 ± 0.45 ng/mg; WKY females, 2.21 ± 0.08 ng/mg, P < 0.05, compared with SHR). Tempol reduced IsoP in SHR to levels found in WKY rats, but had no effect on IsoP in WKY rats.Development of hypertension in SHR is mediated in part by oxidative stress independent of sex. Also, tempol is effective in reducing blood pressure in females only when given prior to the onset of hypertension.