Studies on vasorelaxation by tetrapentylammonium ions in rat aortic rings

Tetrapentylammonium ions (TPA⁺) relaxed the isolated rat aortic rings precontracted with phenylephrine and high extracellular K⁺ in a concentration-dependent manner with respective IC₅₀ values of 38.9 ± 3.9 μM and 40.2 ± 2.9 μM Other quaternary ammonium ions with a carbon side chain of varying length did not induce relaxation. The relaxant effect of TPA⁺ was independent of the presence of the endothelium, and was unaffected by various putative blockers of K⁺ channels such as iberiotoxin (100 nM), glibenclamide (3 μM) and 4-aminopyridine (1 mM). In addition, tetrodotoxin (3 μM), indomethacin (10 μM) and methylene blue (10 μM) had no effect on the TPA⁺-induced relaxation. TPA⁺ (50 μM) and procaine (10 mM) completely abolished the phasic contractile response to caffeine in Ca²⁺-free solution. In the absence of extracellular Ca²⁺, phorbol 12,13-diacetate (PDA) evoked a sustained tension and TPA⁺ concentration-dependently reduced the contraction with IC₅₀ of 30.7 ± 3.1 μM. TPA⁺ reduced the sustained tension of the similar magnitude induced by phenylephrine, 60 mM K⁺ and active phorbol ester with similar potencies. These results indicate that TPA⁺ could act as non-selective relaxant in arterial smooth muscle. This vasorelaxant effect is unique for TPA⁺ since other quaternary ammonium ions did not show the similar action in the rat aorta.