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

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 BK_Ca channel blocker TEA (1 mM), ATP-sensitive potassium (K_ATP) channel blocker glibenclamide (10 µM), and inward-rectifier potassium (K_IR) channel blocker BaCl₂ (30 µM) did not significantly affect kaempferol-induced relaxation. However, inhibition with the voltage-gated potassium (K_V) channel blocker 4-aminopyridine (3 mM) significantly reduced the relaxation response, indicating the involvement of K_V channels. Furthermore, molecular analysis using RT-PCR confirmed the presence of the K_V 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 K_V 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.