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Gender differences in myogenic tone in superoxide dismutase knockout mouse: animal model of oxidative stress

¹Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; and ²Maternal and Fetal Health Research Centre, University of Manchester, Manchester M13 0JH, United Kingdom

Submitted 15 December 2003 ; accepted in final form 12 February 2004

Oxidative stress mediated by prooxidants has been implicated in the pathogenesis of vascular disorders. However, the effect of prooxidants on myogenic regulation of vascular function and the differential influence of gender is not known. SOD, an intracellular enzyme, restricts excess prooxidant levels and may limit vascular dysfunction. We therefore tested the effects of Cu,Zn SOD deficiency on vascular tone in both male and female SOD knockout (SOD–/–) mice. We hypothesized that myogenic tone would be enhanced in SOD–/– mice by excess prooxidants compared with wild-type control mice. Indeed, resistance-sized mesenteric arteries from SOD–/– mice exhibited enhanced myogenic tone compared with control mice. Myogenic tone was lower in female than male control mice. Interestingly, this gender effect was absent in SOD–/– mice, such that myogenic tone of mesenteric arteries from females was equated to that of arteries from males. Furthermore, the pathways that modulate myogenic tone were diverse. In both male and female control mice, inhibition of prostaglandin H synthase (PGHS) and nitric oxide synthase (NOS) pathways enhanced myogenic tone. In female SOD–/– mice, inhibition of PGHS and NOS pathways enhanced myogenic tone to a greater extent compared with control mice. Conversely, in male SOD–/– mice, NOS and PGHS inhibition did not alter tone and only inhibition of gap junctions enhanced myogenic tone. In conclusion, this study revealed enhanced myogenic tone in SOD–/– mice compared with control mice. Furthermore, Cu,Zn SOD deficiency particularly enhanced myogenic tone in female mice such that their vascular tone attained the level of male SOD–/– mice, possibly mediated by prooxidants.

vascular tone; genetic mouse model; sex

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