Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

Abstract

Resveratrol (3, 4', 5-trihydroxy-trans-stilbene) is a natural, non-flavonoid polyphenol that exerts protective properties against atherosclerosis-associated endothelial dysfunction and senescence. The present study aimed to assess the influence of resveratrol on vascular contractility and molecular factors including sirtuin-1 (SIRT1), adiponectin and calprotectin (S100A8/A9) that are considered to be important elements of atherogenesis. A total of 17 male rats were divided into a control and treatment group and administered resveratrol or a placebo. Pharmacometrics were performed on an isolated and perfused tail artery. Serum SIRT1, adiponectin and S100A8/A9 levels were quantified using an ELISA assay. The level of SIRT1 in the control and treatment groups at time 0 was 4.26 and 4.45 ng/ml, respectively. SIRT1 in the control and treatment groups following 2 weeks of treatment was 4.59 and 6.86 ng/ml, respectively (P<0.05) and following 4 weeks of treatment was 4.15 and 6.38 ng/ml, respectively (P<0.05). The level of adiponectin in the control and treatment groups at time 0 was 1.24 and 1.21 ng/ml, respectively. Following 2 weeks of treatment, the level of adiponectin in the control and treatment groups was 1.22 and 1.2 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 1.26 and 1.58 ng/ml, respectively (P<0.05). The S100A8/A9 level in control and treatment groups at time 0 was 0.39 and 0.33 ng/ml, respectively. The level of S100A8/A9 in control and treatment groups following 2 weeks of treatment was 0.37 and 0.35 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 0.34 and 0.32 ng/ml, respectively (P>0.05). EC₅₀ values obtained for phenylephrine in resveratrol-pretreated arteries were significantly higher than controls in the presence and absence of A7-hydrochloride (P<0.05). The results of the present study indicate a significant increase in the concentration of SIRT1 and adiponectin in the resveratrol-pretreated group (P<0.05). S100A8/A9 serum concentrations remained unchanged. Reactivity of resistant arteries was significantly reduced for resveratrol-pretreated vessels and this effect was partially independent of phosphodiesterase (PDE1). Additionally, there was a synergistic interaction observed between resveratrol and the PDE1 inhibitor.

Keywords: S100A8/A9; adiponectin; phosphodiesterase-1; resveratrol; sirtuin-1; vascular smooth muscle cells.

Figure 1.

Concentration of SIRT1 in the serum of control and treatment groups, at time 0 and following 2 and 4 weeks of treatment. Data are presented as mean ± standard deviation. *P=0.026 and **P=0.011 vs. control. SIRT1, sirtuin-1.

Figure 2.

Serum adiponectin concentration in control and treatment groups, at time 0 and following 2 and 4 weeks of treatment. Data are presented as mean ± standard deviation. *P=0.026 vs. control.

Figure 3.

Serum S100A8/A9 concentration in control and treatment groups at time 0 and following 2 and 4 weeks of treatment. Data are presented as mean ± standard deviation. P>0.05. S110A8/A9, calprotectin.

Figure 4.

Concentration-response curves in arteries with vascular endothelium obtained for PHE in the resveratrol-pretreated group in the presence of A7-hydrochloride, PHE control and PHE/A7 hydrochloride control. Data are presented as mean ± standard deviation. For values between 20–80%, P<0.05. *P<0.001 vs. control. PHE, phenylephrine; E_max, maximal response.

Figure 5.

Perfusion pressure in arteries of the resveratrol pretreated group in the presence of A7-hydrochloride, PHE control and PHE/A7 hydrochloride control. Data are presented as mean ± standard deviation. *P<0.05 vs. control. PHE, phenylephrine.