Abstract: AimTo investigate the effects of iptakalim, a new structural potassium channel opener (KCO), on intracellular calcium concentration (［Ca²⁺］_i), protein kinase C (PKC), and cAMP-dependent kinase (PKA) activities in rat tail artery smooth muscle cells (RTA-SMC), and to analyze mechanisms involved in iptakalim reversing hypertensive vascular remodeling. MethodsRTA-SMC was cultured and passages 3-4 were used for experiment. ［Ca²⁺］_i was measured by laser scanning confocal microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and activities of PKA and PKC were detected by commercial assay kits (the nonradioactive PepTag system) following instructions. ResultsCompared with baseline, ［Ca²⁺］_i reduced significantly after iptakalim- or pinacidil-treatment at concentrations of 0.1, 1 and 10 μmol·L^-1, while diazoxide caused significant decrease at concentration of 1 and 10 μmol·L^-1. After preincubation with 1 μmol·L^-1 glibenclamide, ［Ca²⁺］_i was not significantly changed when iptakalim, pinacidil or diazoxide were added at concentration of 0.1 and 1 μmol·L^-1. Activities of PKA and PKC increased significantly by 1 μmol·L^-1 iptakalim- or pinacidil-treatment, while 1 μmol·L^-1 diazoxide induced significant change in activity of PKC but not in that of PKA. ConclusionThe characteristics of iptakalim on ［Ca²⁺］_i, PKA and PKC are more or less similar to those of pinacidil. Iptakalim decreased ［Ca²⁺］_i while increased PKA and PKC activities of RTA-SMCs, which may contribute to its ability to reverse antihypertensive vascular remodeling.