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Treatment with high dose of atorvastatin reduces vascular injury in diabetic rats
Fabiana Vieira Simões1, Priscila Rossi de Batista1, Tatiani Botelho1
1Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil.
Background:
Previous reports showed conflicting results regarding the treatment effects of statin on Diabetes mellitus (DM). We investigated how treatment with high dose of atorvastatin affects the impaired vascular function in diabetic rats.
Methods:
Atorvastatin (80mg/kg/day, oral gavage, 4 weeks) or its vehicle was administered to male control or streptozotocin (STZ)-induced diabetic rats. Aortic segments were used to investigate the vascular reactivity, protein expression of cyclooxygenase-2 (COX-2) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) 1 (NOX1) and superoxide anions levels.
Results:
Atorvastatin treatment did not affect glycemia levels. In diabetic rats, the vascular reactivity to phenylephrine increased compared with controls and the atorvastatin treatment reduced this response. Removal of the endothelium increased the response to phenylephrine in control rats, but not in the diabetic group. Atorvastatin increased the endothelial modulation in diabetic rats. L-NAME (100μM) increased the reactivity in all groups, but this effect was greater in atorvastatin-treated diabetic rats. Indomethacin (10μM) and NS398 (1μM) decreased the contractile response in diabetic rats and atorvastatin reversed these effects, without changing COX-2 expression. Apocynin (30μM) decreased the phenylephrine response in diabetic rats, which also showed increased NOX1 and superoxide anions; these effects were prevented by atorvastatin treatment.
Conclusions:
The results suggest that treatment with high dose of atorvastatin, independent of glycemia, improves endothelial function in aortas from diabetic rats by reducing the constrictor prostanoids derived from COX-2 and by reducing the oxidative stress by NADPH oxidase, as well as a possible increasing of nitric oxide participation.
Insights
High-dose atorvastatin improves vascular function in diabetic rats by reducing oxidative stress and constrictor prostanoids, independent of blood sugar control. This study highlights atorvastatin
Area of Science:
- Pharmacology
- Cardiovascular Biology
- Metabolic Disorders
Background:
- Conflicting reports exist on statin efficacy in diabetes mellitus (DM).
- Vascular dysfunction is a key complication of diabetes.
- High-dose atorvastatin's effect on diabetic vascular function requires clarification.
Purpose of the Study:
- To investigate the impact of high-dose atorvastatin on vascular function in streptozotocin (STZ)-induced diabetic rats.
- To elucidate the mechanisms underlying atorvastatin's effects on vascular reactivity and oxidative stress.
Main Methods:
- Diabetic rats received high-dose atorvastatin (80mg/kg/day) or vehicle for 4 weeks.
- Vascular reactivity of aortic segments was assessed.
- Protein expression of cyclooxygenase-2 (COX-2) and NADPH oxidase 1 (NOX1), and superoxide anion levels were measured.
Main Results:
- Atorvastatin did not alter glycemia but improved vascular reactivity in diabetic rats.
- It reduced phenylephrine-induced contraction, enhanced endothelial modulation, and counteracted effects of L-NAME, indomethacin, and NS398.
- Atorvastatin treatment prevented increased NOX1 and superoxide anion levels in diabetic aortas.
Conclusions:
- High-dose atorvastatin improves endothelial function in diabetic rat aortas, independent of glycemic control.
- This improvement is achieved by reducing COX-2 derived constrictor prostanoids and NADPH oxidase-mediated oxidative stress.
- A potential increase in nitric oxide participation may also contribute to the observed benefits.
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