EFFECTS OF FLECAINIDE ON ISOLATED VASCULAR SMOOTH MUSCLES OF RAT

1 The inhibitory effects of flecainide were studied on contractile responses in rat isolated aortae and caudal artery and on spontaneous mechanical activity in portal vein segments. 2 In rat isolated aorta flecainide, 10(-6) M-5 x 10(-4) M, inhibited in a dose-dependent manner the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M). These inhibitory actions were observed when flecainide was added before or after the induced contractions and were similar in aortae with or without endothelium. 3 Contractile responses induced by addition of Ca to Ca-free high-K solution were also dose-dependently inhibited by flecainide (IC50 = 2.5 +/- 0.3 x 10(-5) M). Moreover, flecainide inhibited the contractile responses elicited by NA in rings incubated in Ca-free solution. 4 Flecainide also inhibited the spontaneous mechanical activity in portal vein segments (IC50 = 6.5 +/- 0.9 x 10(-5) M). 5 Flecainide, 10(-4) M, inhibited Ca-45 uptake stimulated by high K or NA without altering Ca-45 uptake in resting aortae. 6 These results indicated that in rat isolated aortae, caudal arteries and portal veins, flecainide inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores, thus decreasing the availability of intracellular free Ca required for vascular smooth muscle contraction.