Abstract
Tetrapentylammonium ions (TPA +) relaxed the isolated rat aortic rings precontracted with phenylephrine and high extracellular K + in a concentration-dependent manner with respective IC 50 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 Ca 2+-free solution. In the absence of extracellular Ca 2+, phorbol 12,13-diacetate (PDA) evoked a sustained tension and TPA + concentration-dependently reduced the contraction with IC 50 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 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.
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