Abstract:

This study aimed to determine the functional effects and mechanisms of action of pravastatin, a cholesterol-lowering drug, in rat thoracic aorta. Vessel segments isolated from the thoracic aortas of male Wistar Albino rats were placed in chambers within an isolated tissue bath system. The resting tension was set to 1 g. After an equilibration period, the thoracic aorta rings were contracted with 10-6 M phenylephrine. Once a steady contraction was obtained, cumulative pravastatin (10-8-10-4 M) was applied to the vascular rings. To identify the vasoactive effect mechanisms of pravastatin, the specified experimental protocol was repeated after incubation with specific signaling pathway inhibitors and potassium channel blockers. Pravastatin showed a concentration-dependent relaxation in precontracted rat thoracic aorta rings (p<0.001). The vascular relaxant effect levels of pravastatin were significantly reduced by removal of the endothelium, L-NAME application, and indomethacin incubation (p<0.001). Pravastatin-induced vasorelaxation levels were also significantly reduced following TEA, 4-Aminopyridine, XE-991, apamin, dorsomorphin, and anandamide administrations (p<0.001). However, applications of glyburide and barium chloride did not cause a statistically significant change in the vasorelaxant effect level of pravastatin (p=1.000). Pravastatin has a prominent vasorelaxant effect in rat thoracic aorta. Intact endothelium, nitric oxide, prostanoids, AMPK, and potassium channels (BKCa, SKCa, KV, and K2p channels) play a role in the vascular relaxant effect of pravastatin.

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