Gender differences and antioxidant treatment affect aortic reactivity in short-term diabetic rats.
Diabetes is associated with gender-specific macrovascular complications arising from increased oxidant stress in the vascular wall. In this study, male and female rats were treated with two structurally unrelated drugs sharing antioxidant properties, lercanidipine and Leucoselect (both 3 mg/kg/day), for 1 week starting 1 day after streptozotocin-diabetes induction. Concentration-response curves to L-nitroarginine methylester (L-NAME), superoxide dismutase and acetylcholine in aortic rings showed significantly greater nitric oxide-mediated relaxation in female compared with male non-diabetic rats. Diabetes increased contractility to noradrenaline and L-NAME in both genders, whereas relaxation to acetylcholine and iloprost were significantly attenuated in females only. Treatment with lercanidipine and Leucoselect restored, at least in part, responses to noradrenaline, acetylcholine and iloprost without affecting those to L-NAME and sodium nitroprusside. Unexpectedly, both drugs impaired superoxide dismutase response in female tissues. In conclusion, female rat aorta is markedly exposed to short-term diabetic vascular injury, which may be prevented by antioxidant treatment.
Pinna
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C
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Christian.Pinna@unimi.it
Cignarella
A
A
Zanardo
R
R
Bolego
C
C
Puglisi
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D001786:Blood Glucose; D004095:Dihydropyridines; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D016285:Iloprost; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; C060343:lercanidipine; D009638:Norepinephrine