Apigenin relaxes rat intrarenal arteries, depresses Ca2+-activated Cl− currents and augments voltage-dependent K+ currents of the arterial smooth muscle cells

Abstract

The vasorelaxant effect of apigenin (API) has been demonstrated in a number of vascular beds. We aimed to study the possible involvement of Cl− channels and K+ channels in API-induced vasorelaxation in intrarenal arteries. The vascular tone of isolated rat intrarenal arteries (RIRAs) was measured with a myograph. The myocyte transmembrane Cl− currents through Ca2+ activated Cl− channels (CaCCs) and the K+ currents through voltage-dependent (Kv) K+ channels were recorded using a patch clamp in the single arterial smooth muscle cells (ASMCs) isolated freshly from RIRAs. Preincubation with API (10–100 μM) concentration-dependently depressed the contractions induced by KCl, thromboxane A2 analog U46619, phenylephrine and vasopressin. The IC50 values were 13.27–26.26 μM. Instant application of API elicited immediate relaxations in RIRAs precontracted with these vasoconstrictors. The RC50 values were 5.80–24.33 μM. Chloride deprivation, Cl− channel blockers, Kv blocker and nitric oxide synthase inhibitor attenuated API-induced RIRA relaxation. At 10–100 μM, API depressed CaCC currents, but augmented Kv currents. Taken together, the present study demonstrated that API depresses contractions induced by various vasoconstrictors in RIRAs, suppresses CaCC currents and augments Kv currents in RIRA ASMCs.