2024-10-222024-10-222023-09-251098-8823https://doi.org/10.1016/j.prostaglandins.2023.106782https://hdl.handle.net/11452/46855Objective: This study aimed to investigate vasoactive effect mechanisms of cilostazol in rat thoracic aorta.Materials and methods: The vessel rings prepared from the thoracic aortas of the male rats were placed in the chambers of the isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration phase, potassium chloride or phenylephrine was used to contract the vessel rings. When achieving a steady contraction, cilostazol was applied cumulatively (10(- 8)-10(-4) M). In the presence of potassium channel blockers or signaling pathway inhibitors, the same experimental procedure was performed.Results: Cilostazol exhibited a significant vasorelaxant effect in a concentration-dependent manner (pD2: 5.94 +/- 0.94) (p < .001). The vasorelaxant effect level of cilostazol was significantly reduced by the endothelial nitric oxide synthase inhibitor L-NAME (10(-4) M), soluble guanylate cyclase inhibitor methylene blue (10 mu M), cyclooxygenase 1/2 inhibitor indomethacin (5 mu M), adenosine monophosphate-activated protein kinase inhibitor compound C (10 mu M), non-selective potassium channel blocker tetraethylammonium chloride (10 mM), large -conductance calcium-activated potassium channel blocker iberiotoxin (20 nM), voltage-gated potassium channel blocker 4-Aminopyridine (1 mM), and inward-rectifier potassium channel blocker BaCl2 (30 mu M) (p < .001). Moreover, incubation of cilostazol (10(-4) M) significantly reduced caffeine (10 mM), cyclopiazonic acid (10 mu M), and phorbol 12-myristate 13-acetate-induced (100 mu M) vascular contractions (p < .001).Conclusions: In the rat thoracic aorta, the vasodilator action level of cilostazol is quite noticeable. The vaso-relaxant effects of cilostazol are mediated by the eNOS/NO/cGMP pathway, prostanoids, AMPK pathway, PKC, potassium channels, and calcium channels.eninfo:eu-repo/semantics/closedAccessDual antiplatelet therapyResistance arteriesCyclopiazonic acidProtein-kinaseSmooth-muscleInhibitorVasodilationImplantationEndotheliumOutcomesAmpkAortaCilostazolNitric oxidePotassiumTissue bathScience & technologyLife sciences & biomedicineBiochemistry & molecular biologyCell biologyArticle00108657230000116910.1016/j.prostaglandins.2023.106782