Relaxant Effect of Rosuvastatin in Isolated Rat Aorta with Perivascular Adipose Tissue

Objective: Rosuvastatin displays favorable pleiotropic effects on vascular system to reduce the risk of cardiovascular events besides providing an intensive reduction in LDL-C levels. The role of perivascular adipose tissue (PVAT) in modulating the vasorelaxant effect of rosuvastatin is not evaluated so far. The present study aimed to investigate the vascular relaxant effect of rosuvastatin in rat aortic rings with intact PVAT, as well as to evaluate the possible mechanisms underlying this effect in relation to nitric oxide (NO) and prostaglandin pathways. Methods: Thoracic aorta rings with intact PVAT, isolated from male Wistar rats (n=5), were mounted on an isolated organ bath system. Endothelium-dependent responses to acetylcholine (Ach,10-6-10-4M) were obtained in aortic rings precontracted submaximally with phenylephrine (Phe,10-6-3x105M). The concentration-dependent relaxant effect of rosuvastatin (10-7-10-4M) was examined in the absence and presence of NO inhibitor, L-NOARG (10-4M, 30min.) and cyclooxygenase inhibitor, indomethacin (10-5M, 30min.). Vascular relaxation capacity of aortic rings was checked by the nitrovasodilator, sodium nitroprusside (SNP,10-6 M) at the end of the experiments. Results: Rosuvastatin (10-7-10-4M) produced concentration-dependent relaxations in Phe-precontracted rat aortic rings with intact PVAT. Pretreatment with L-NOARG significantly attenuated the relaxant responses to rosuvastatin in isolated rat aortic rings with intact PVAT. However, pretreatment with indomethacin did not modify the relaxations to rosuvastatin. In the aortic rings, maximal relaxation responses to Ach and SNP were determined to be 75.87±2.68% and 102.54±2.92%, respectively. Conclusions: This study will provide a basis for investigating the interaction between PVAT and statins in vascular homeostasis.