Cardiovascular effects of resveratrol and atorvastatin treatments in an H2O2-induced stress model

Abstract

Oxidative stress has been implicated in the pathophysiology of several types of cardiovascular disease (CVD). Statins are widely used to inhibit the progression of atherosclerosis and reduce the incidence of CVD. Certain over-the-counter products, including resveratrol, show similar effects to statins and may thus be used in conjunction with statins for the treatment of the majority of patients with CVD. The aim of the present study was to evaluate the effects of atorvastatin, resveratrol and resveratrol + atorvastatin (R+A) pretreatment on myocardial contractions and vascular endothelial functions in the presence of H₂O₂ as an experimental model of oxidative stress in rats. Four groups were established and referred to as the control, atorvastatin, resveratrol and R+A groups. Atorvastatin (40 mg/kg, per oral) and/or resveratrol (30 mg/kg, intraperitoneal) treatments were administered for 14 days. On the 15th day, the thoracic aortas and hearts of the rats were dissected and placed into isolated organ baths. Vascular responses to cumulative doses of H₂O₂ (1×10^-8-1×10^-4 M H₂O₂) with and without N (G)-nitro-L-arginine methyl ester (L-NAME) incubation were measured. In addition, myocardial electrical stimulation (ES) responses to various H₂O₂ concentrations (1×10^-7-1×10^-5 M H₂O₂) were evaluated. In the control and atorvastatin groups, H₂O₂ application caused a significant dose-dependent decrease in the ES-induced contractions in the myocardial tissue of rats. In the resveratrol and R+A groups, H₂O₂ application did not significantly affect myocardial contraction at any dose. In all groups, incubation with L-NAME caused a significant augmentation in the H₂O₂ response, revealing that this effect was mediated via the vascular endothelium. In conclusion, pretreatment with R+A for CVD appears to be superior to pretreatment with either agent alone.

Keywords: atorvastatin; endothelium; hydrogen peroxide; myocardium; resveratrol.

Figure 1

(A) Effects of ES with 1×10⁻⁷ M H₂O₂ on rat myocardium.^*P<0.01 vs. control group; ^#P<0.01 vs. resveratrol group. (B) Myocardial effects of ES with 1×10⁻⁶ M H₂O₂. ^*P<0.05 vs. control group; ^#P<0.01 vs. resveratrol group. (C) Myocardial effects of ES with 1×10⁻⁵ M H₂O₂. ^*P<0.05 vs. control group; ^#P<0.05 vs. R+A group; ^**P<0.01 vs. resveratrol group. ES, electrical stimulation; R+A, resveratrol + atorvastatin.

Figure 2

(A) Cumulative contractile response elicited by H₂O₂ (1×10⁻⁸–1×10⁻⁴ M) in aorta segments. ^*P<0.05 vs. treatment groups. (B) The same procedure but showing results following 30 min incubation with 1×10⁻⁴ M L-NAME. R+A, resveratrol + atorvastatin; L-NAME, N (G)-nitro-L-arginine methyl ester.

Figure 3

Effect of cumulative concentrations of H₂O₂ on basal tone. Comparison between incubation of aortic segments with and without L-NAME in the (A) control, (B) atorvastatin-treated, (C) resveratrol-treated and (D) R+A-treated groups. R+A, resveratrol + atorvastatin; L-NAME, N (G)-nitro-L-arginine methyl ester.