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 microM and 40.2 +/- 2.9 microM. 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 microM) and 4-aminopyridine (1 mM). In addition, tetrodotoxin (3 microM), indomethacin (10 microM) and methylene blue (10 microM) had no effect on the TPA+-induced relaxation. TPA+ (50 microM) 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 microM. 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 a 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.