Chrysin, a natural flavonoid available in honey, propolis and medicinal plants, has been shown to be vasorelaxant in some vascular beds. Proper intake of an alimental vasodilator as a food additive may be a promising strategy for prevention and treatment of coronary spasmodic disorders. TMEM16A-encoded anoctamin 1 (ANO1), a Ca²⁺ activated Cl^- channel (CaCC), plays an important role in the modulation of vascular tone. We tested the possibility that inhibition of CaCCs contributes to chrysin-induced coronary arterial relaxation. The vascular tone of the rat coronary artery (RCA) was recorded with a wire myograph. CaCC currents were assessed using whole-cell patch clamp in arterial smooth muscle cell (ASMC) freshly isolated from RCAs. An inhibitor study was performed to explore the mechanisms underlying the vasomotor and electrophysiological effects of chrysin. Pre-incubation with chrysin depressed the contractions elicited by thromboxane A2 analog U46619, vasopressin (VP), depolarization and extracellular Ca²⁺ elevation/depolarization without significant preference among these vasoconstrictors. Besides, chrysin inhibited both intracellular Ca²⁺ release-dependent and extracellular Ca²⁺ influx-dependent components of contractions induced by U46619 or VP. In RCAs pre-contracted with U46619, VP or KCl, chrysin elicited concentration-dependent relaxations, which were weakened by Cl^- -deprivation. The electrophysiological study showed that chrysin reduced ANO1-antibody-sensitive CaCC currents and depressed CaCC increments induced by U46619. Inhibitor study showed that both the vasorelaxation and the CaCC current reduction induced by chrysin were attenuated by blocking CaCCs and inhibiting cAMP/PKA and NO/PKG pathways. The present findings indicate that inhibition of RCA ASMC CaCC currents, which may be consequential following intracellular Ca²⁺ availability reduction and activation of cAMP/PKA and NO/cGMP signaling pathways, contributes to chrysin-induced RCA relaxation.

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.

The vasodilator effect of apigenin (API) was demonstrated in a number of vascular beds. We aimed to characterize the vasospasmolytic and electrophysiological effects of apigenin (API) in intrarenal arteries (IRAs). The vascular tone of male rat isolated IRAs was recorded with a myograph. Transmembrane Cl ⁻ currents through Ca ²⁺ -activated Cl ⁻ channels (CaCCs), K ⁺ currents through voltage-gated K ⁺ (Kv) channels and inwardly rectifier K ⁺ (Kir) channels were recorded with patch clamp in the freshly isolated arterial smooth muscle cells (ASMCs). Preincubation with API (10-100 μM) concentration-dependently depressed the contractions induced by KCl, 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F _2α (U46619), phenylephrine and vasopressin without significant preference and the IC ₅₀ values were 13.27-26.26 μM. Acute application of API elicited instant relaxations in the IRAs precontracted with these vasoconstrictors and the RC ₅₀ values were 5.80-24.33 μM. API relaxation was attenuated by chloride deprivation, CaCC blockers, Kv blocker and nitric oxide synthase inhibitor, but not by Kir blocker and cyclooxygenase inhibitor. At 10-100 μM, API depressed CaCC currents and Kir currents while enhanced Kv currents of IRA ASMCs. The present results demonstrate that API counteracts various vasoconstrictors noncompetitively and nonspecifically and suggest that modulation of CaCCs, Kv and Kir channels of IRA ASMCs is involved in its vasospasmolytic effects.