Gender differences and antioxidant treatment affect aortic reactivity in short-term diabetic rats

Diabetes is associated with gender-specific macrovascular complications ari sing from increased oxidant stress in the vascular wall. In this study, mal e and female rats were treated with two structurally unrelated drugs sharin g antioxidant properties, lercanidipine and Leucoselect((TM)) (both 3 mg/kg /day), for 1 week starting 1 day after streptozotocin-diabetes induction. C oncentration-response curves to L-nitroarginine methylester (L-NAME), super oxide dismutase and acetylcholine in aortic rings showed significantly grea ter nitric oxide-mediated relaxation in female compared with male non-diabe tic rats. Diabetes increased contractility to noradrenaline and L-NAME in b oth genders, whereas relaxation to acetylcholine and iloprost were signific antly attenuated in females only. Treatment with lercanidipine and Leucosel ect restored, at least in part, responses to noradrenaline, acetylcholine a nd iloprost without affecting those to L-NAME and sodium nitroprusside. Une xpectedly, both drugs impaired superoxide dismutase response in female tiss ues. In conclusion, female rat aorta is markedly exposed to short-term diab etic vascular injury, which may be prevented by antioxidant treatment. (C) 2001 Elsevier Science B.V. All rights reserved.