Kaempferol Promotes Vasorelaxation via KV 2.1 Channel Modulation in the Coronary Arteries of Sheep

Abstract

Kaempferol, a flavonol found in various edible and medicinal plants, possesses antioxidant, anti-inflammatory, and cardioprotective properties. The vasorelaxant effects of kaempferol were assessed using isolated coronary artery rings pre-contracted with potassium chloride (30 mM). Kaempferol induced a concentration-dependent relaxation in both endothelium-intact and endothelium-denuded coronary artery rings pre-contracted with potassium chloride (30 mM), indicating that its vasorelaxant effect is primarily endothelium-independent. Inhibition of nitric oxide synthase (NOS) with L-NAME (100 μM) and cyclooxygenase (COX) with indomethacin (10 μM) did not significantly alter the relaxation response, suggesting that nitric oxide (NO) and prostaglandins play a minimal role. The BKCa channel blocker TEA (1 mM), ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 μM), and inward-rectifier potassium (KIR) channel blocker BaCl2 (30 μM) did not significantly affect kaempferol-induced relaxation. However, inhibition with the voltage-gated potassium (KV) channel blocker 4-aminopyridine (3 mM) significantly reduced the relaxation response, indicating the involvement of KV channels. Furthermore, molecular analysis using RT‑PCR confirmed the presence of the KV 2.1 (KCNB1) gene in sheep coronary arteries, suggesting its role in kaempferol-mediated vasorelaxation. These findings suggest that kaempferol promotes vasorelaxation through an endothelium-independent mechanism, with partial involvement of the KV 2.1 channel. This study supports kaempferol's therapeutic potential in cardiovascular disease, recommending its dietary inclusion as a strategy to lower the risk of cardiovascular diseases.