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Gender differences and antioxidant treatment affect aortic reactivity in short-term diabetic rats
C Pinna1, A Cignarella, R Zanardo
1Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Christian.Pinna@unimi.it
Abstract:
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.
Insights
Antioxidant drugs like lercanidipine and Leucoselect may protect female rats from short-term diabetes-induced vascular injury, restoring blood vessel function. These findings highlight potential therapeutic strategies for diabetic complications.
Area of Science:
- Vascular Biology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is linked to gender-specific macrovascular complications.
- Increased oxidant stress in the vascular wall contributes to these complications.
Purpose of the Study:
- To investigate the protective effects of antioxidant drugs, lercanidipine and Leucoselect, against short-term diabetic vascular injury in a gender-specific manner.
- To evaluate the impact of these antioxidants on vascular reactivity in male and female diabetic rats.
Main Methods:
- Male and female rats were induced with diabetes using streptozotocin.
- Treated with lercanidipine or Leucoselect (3 mg/kg/day) for one week.
- Vascular responses to various agents (L-NAME, superoxide dismutase, acetylcholine, noradrenaline, iloprost) were assessed in aortic rings.
Main Results:
- Female non-diabetic rats exhibited greater nitric oxide-mediated relaxation than males.
- Diabetes attenuated acetylcholine and iloprost relaxation in females and increased noradrenaline/L-NAME contractility in both genders.
- Antioxidant treatment partially restored responses to noradrenaline, acetylcholine, and iloprost.
- Both drugs unexpectedly impaired superoxide dismutase response in female tissues.
Conclusions:
- Female rat aorta is highly susceptible to short-term diabetic vascular injury.
- Antioxidant treatment demonstrates potential in preventing or mitigating these injuries.
- Further research is needed to understand the gender-specific mechanisms and drug interactions.