Luteolin-induced coronary arterial relaxation involves activation of the myocyte voltage-gated K+ channels and inward rectifier K+ channels

Abstract

Aims: Luteolin has been shown to be beneficial to cardiovascular tissues and organs. We aimed to study its vasospasmolytic effects against various vasoconstrictors in the isolated rat coronary arteries (RCAs) and its electrophysiological effects on K⁺ currents via voltage-gated potassium (Kv) channels and inward rectifier potassium (Kir) channels in freshly isolated rat coronary arterial smooth muscle cells (RCASMCs).

Main methods: The vascular tone of the endothelium-denuded RCAs was recorded by a wire myograph. Kv currents and Kir currents in RCASMCs were assessed using whole-cell patch clamp.

Key findings: Preincubation with luteolin depressed the contractions elicited by KCl, thromboxane A₂ analog U46619, vasopressin, Kir blocker BaCl₂, Kv blocker 4-aminopyridine and elevation of extracellular calcium ([Ca²⁺]_o) in high K⁺ depolarizing solution. Instant application of luteolin produced concentration-dependent relaxations in the endothelium-denuded RCAs precontracted with KCl or U46619. Both 4-aminopyridine and BaCl₂ attenuated luteolin-induced relaxation in U46619-precontracted RCAs, while neither nitric oxide synthetase inhibitor NG-nitro-L-arginine methyl ester nor cyclooxygenase inhibitor indomethacin affected the relaxation. Luteolin augmented both Kv currents and Kir currents in RCASMCs and the augmentations were antagonized by 4-aminopyridine and BaCl₂, respectively.

Significance: The present results demonstrated that luteolin antagonizes various vasoconstrictors in RCAs and augments both Kv currents and Kir currents in RCASMCs, suggesting that the direct action of luteolin on Kv channels and Kir channels is contributory to its vasospasmolytic effect. These findings indicate that luteolin may be a promising food additive with the aim of preventing coronary arterial spasm.

Keywords: Coronary artery; Inward rectifier potassium channel; Luteolin; Vasorelaxation; Voltage-gated potassium channel.