Effects of propafenone on ⁴⁵Ca movements and contractile responses in vascular smooth muscle

Abstract

1 In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose-dependently inhibited the contractile responses induced by high K (80mM) and noradrenaline (NA, 10-SM), the ICSos being 2.5 + 0.7 x 10-6 M and 8.7 + 0.8 x 10-6 M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2 Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 + 0.8 x 10-6M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 + 0.9 X 106M). 3 Propafenone also inhibited (IC50 = 1.2 + 0.4 x 10 -M) the development of spontaneous mechanical activity in portal vein segments.4 Propafenone, 5 x 10-6M and 10-SM, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5 These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction.

Effects of flecainide on isolated vascular smooth muscles of rat

“…The results are expressed as a percentage of the maximal contractile response induced by 5 mm CaCl2 . (4) To study the effects of flecainide on a membrane store of Ca mobilized by NA, the experimental protocol employed was similar to that previously described (Ebeibge & Aloamaka, 1985;Carron et al, 1991). Aortic rings incubated in Ca-free KS were stimulated by successive additions of 10-5 M NA for 5min ('Ca-washing').…”

Voltage‐ and time‐dependent inhibitory effects on rat aortic and porcine coronary artery contraction induced by propafenone and quinidine

“…In contrast, the inhibition of 45Ca2+ uptake produced by 3 x 10-6 M propafenone was not different in aortic rings incubated in 5 or 40 mM KCI PSS. (Cauvin et al, 1983;Godfraind et al, 1986 (Carron et al, 1991;Perez-Vizcaino et al, 1991 Fei et al, 1993) and quinidine (pD2 = 5.0. Scamps et al, 1989).…”

“…However, information on the inhibitory effect of antiarrhythmic drugs in vascular smooth muscle is sparse. Recently, it has been found that the inhibitory effect exerted by two class Ic antiarrhythmic drugs, propafenone and flecainide, in rat isolated aorta was accompanied by inhibition of 45Ca2+ influx (Carron et al, 1991;Nrez-Vizcaino et al, 1991). Thus, it is possible that the hypotensive effect of these antiarrhythmic agents may be related to the inhibition '."…”

Design, synthesis and biological activity of phenylpropiofenone aminoalcoxy derivatives

“…U terapijskim koncentracijama, propafenon inhibira i nekoliko K + struja u srcu: I TO Propafenon redukuje postojeću I Ca struju, ali ne utiče na njenu aktivaciju 218 . Ovaj efekat u miocitima pretkomora i komora dovodi do produženog trajanja AP-a i refraktarnog perioda, dok u glatkim mišićima krvnih sudova dovodi do vazodilatacije [219][220][221][222] .…”

“…Efekti propafenona na jonskim kanalima do skora su se zasnivali samo na elektrofiziološkim ili in vitro animalnim modelima [21][22][219][220][221][222]228 . Poslednjih godina QSAR studije sve više dobijaju na značaju i uglavnom su vezane za interakciju sa hERG kanalom 212,214,[244][245] .…”