Comparative vasorelaxant effects of atorvastatin and rosuvastatin in rat aorta: investigating the role of perivascular adipose tissue.

Abstract

Background/aim: Statins are known to display pleiotropic effects on the vascular system, beyond their lipid-lowering properties. Studies on isolated vascular preparations have demonstrated their acute relaxant effects on vascular tone. Considering the increased evidence in regard to the contribution of perivascular adipose tissue (PVAT) in the regulation of vascular homeostasis, we aimed to investigate the possible modulatory role of PVAT in the vascular effects of atorvastatin and rosuvastatin in isolated rat aorta.

Materials and methods: Thoracic aortas isolated from young male Wistar rats were divided into two groups: rings with intact PVAT (+) and rings without PVAT (-), and then mounted in an isolated organ bath system. Rat aortic rings were standardized with potassium chloride (KCl, 40 mM), and then endothelium-dependent relaxation responses were checked by acetylcholine (Ach, 10^-7-10^-4 M). The concentration-dependent (10^-7-10^-4 M) effects of atorvastatin and rosuvastatin were studied on rat aortic rings precontracted submaximally with phenylephrine (Phe, 10^-6-3 × 10^-5 M). In addition, endothelium-independent relaxation responses were evaluated by sodium nitroprusside (SNP, 10^-6 M) at the end of each experiment.

Results: Rat aortic rings with intact PVAT (+) and without PVAT (-) displayed similar endothelium-dependent and -independent relaxations to Ach and SNP, respectively. Increasing concentrations (10^-7-10^-4 M) of atorvastatin and rosuvastatin directly relaxed the aortic rings with and without PVAT. The maximum relaxant effects of rosuvastatin was found significantly greater than atorvastatin.

Conclusion: The current study demonstrated that atorvastatin and rosuvastatin displayed prominent relaxations in rat aortic rings with intact PVAT (+) and without PVAT (-). Notably, rosuvastatin produced a greater vasorelaxant effect compared to atorvastatin in rat aortic rings with and without PVAT. Current study provides a novel evidence that PVAT does not significantly influence statin-mediated vasorelaxation under physiological conditions.