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Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin
A S Dumont1, M E Hyndman, R J Dumont
1Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA. asd2f@virginia.edu
Insights
Pravastatin improved blood vessel function in insulin-resistant rats with high blood pressure. This cholesterol-independent effect may help prevent carotid artery disease by boosting nitric oxide production.
Area of Science:
- Vascular biology
- Endocrinology
- Pharmacology
Background:
- Insulin resistance and hypertension are key stroke risk factors.
- Endothelial dysfunction and carotid artery disease contribute to stroke pathogenesis.
- Pravastatin may offer cholesterol-independent benefits.
Purpose of the Study:
- To investigate pravastatin's effect on endothelial function.
- To assess pravastatin's impact in insulin-resistant rats with hypertension.
- To examine cholesterol-independent pleiotropic effects of pravastatin.
Main Methods:
- Rats were fed a standard or fructose-enriched diet for 3 weeks.
- Pravastatin was administered to control and fructose-fed rats for 2 weeks.
- Vascular reactivity, nitric oxide metabolite excretion, and insulin resistance were assessed.
Main Results:
- Fructose-fed rats showed insulin resistance, hypertension, and impaired endothelium-dependent vasomotion.
- Pravastatin treatment normalized endothelium-dependent vasomotion and nitric oxide metabolite excretion.
- Endothelium-independent vasomotion remained unaffected by fructose or pravastatin.
Conclusions:
- Pravastatin restores endothelial function in insulin-resistant hypertensive rats.
- Benefits are attributed to cholesterol-independent vascular effects, likely via nitric oxide augmentation.
- Further research into non-lipid-lowering uses of pravastatin for carotid artery disease is warranted.
Object:
Insulin resistance and hypertension are independent risk factors for stroke. Endothelial dysfunction in response to risk factors and carotid artery (CA) disease are important in the pathogenesis of stroke. Pravastatin may have cholesterol-independent pleiotropic effects. In the present study the authors examined the effects of short-course pravastatin treatment on endothelial function in CAs obtained in control and insulin-resistant rats with fructose-induced hypertension.
Methods:
Thirty rats were divided into two experimental groups, in which 14 were fed a regular diet and 16 were fed a fructose-enriched diet for 3 weeks. The rats were then divided into four groups: control, pravastatin-treated control, fructose-fed, and pravastatin-treated fructose-fed. Pravastatin was administered (20 mg/kg/day) for 2 weeks. Excretion of the urinary nitric oxide (NO) metabolite nitrite (NO2-) was also assayed. The CAs from all rats were subsequently removed and assessed for endothelium-dependent and -independent vascular reactivity in vitro. The rats in the fructose-fed group were insulin resistant, hyperinsulinemic, and hypertensive relative to the rats in the control and pravastatin-treated control groups and exhibited diminished endothelium-dependent vasomotion and urinary NO2- excretion (p < 0.05), with preserved endothelium-independent vasomotion. Strikingly, pravastatin treatment restored endothelium-dependent vasomotion and urinary NO2- excretion in rats in the fructose-fed pravastatin-treated relative to the fructose-fed group (p < 0.05).
Conclusions:
The authors report, for the first time, that pravastatin restores endothelial function in CAs from insulin-resistant rats with fructose-induced hypertension. These beneficial effects were ascribed to direct, cholesterol-independent vascular effects of pravastatin and are likely the result of augmentation of NO production. These data provide impetus for further investigation of nonlipid-lowering indications for pravastatin therapy in the prevention and treatment of CA disease.