Hesperetin improves diabetic coronary arterial vasomotor responsiveness by upregulating myocyte voltage-gated K⁺...

Hesperetin (HSP) is a naturally occurring flavonoid. The present study aimed to investigate the potential vasomotor effects and mechanisms of HSP action on rat coronary arteries (RCAs) injured by diabetes or high glucose concentrations. HSP (100 mg/kg/day) was intragastrically administered to the rats for 8 weeks, which were rendered diabetic with a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The vascular tone of RCAs was recorded using a wire myograph. The voltage-dependent K⁺ (Kv) currents were examined using patch clamping. The expression of Kv channels (Kv1.2 and Kv1.5) was examined by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). Diabetes induced contractile hypersensitivity and vasodilator hyposensitivity in RCAs, both of which were attenuated by the chronic administration of HSP. Patch clamp data revealed that chronic HSP treatment reduced diabetes-induced suppression of Kv currents in the myocytes. Western blot and RT-qPCR analyses revealed that chronic HSP administration increased the expression of Kv1.2, but not Kv1.5, in the RCAs of diabetic rats compared with those from non-diabetic rats. In vitro analysis showed that co-incubation with HSP ameliorated high-glucose-induced suppression of Kv currents and Kv 1.2 protein expression in the myocytes. Taken together, the present study demonstrated that HSP alleviated RCA vasomotor dysfunction as a result of diabetes in rats by upregulating the expression of myocyte Kv channels.