The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta

Abstract

The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.

Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja.