Endothelium-dependent relaxation by tetraoctylammonium ions in rat isolated aortic rings

Quaternary ammonium ions are common pharmacological blockers of K⁺ channels. This study examined the vasorelaxant effect of tetraoctylammonium ions (TOA⁺) in rat isolated aortic rings. TOA⁺ caused a concentration-dependent transient relaxation of endothelium-intact tissues. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 3x10^-5 M) or methylene blue (3x10^-6 M) or removal of the endothelium abolished the TOA⁺-induced relaxation. L-arginine (10^-3 M) partially antagonized the effect of L-NAME. Glibenclamide (3x10^-6 M), charybdotoxin (CTX, 10^-7 M), indomethacin (10^-5 M), or atropine (3 x 10^-6 M) had no effect. Both TOA⁺ (10^-5 M)- and acetylcholine (ACh, 10^-5 M)-induced increase in tissue content of cyclic GMP was significantly attenuated by N(G)-nitro-L-arginine (L-NNA, 10^-4 M) and abolished in endothelium-denuded arteries. These results indicate that TOA⁺ induced endothelium-dependent relaxation which is likely mediated through nitric oxide but not other endothelium-derived factors. This relaxant action seems unique for TOA⁺ since other quaternary ammonium ions did not cause nitric oxide-dependent relaxation.