Effects of different tetra-n-alkylammonium ions on acetylcholine-induced endothelium-dependent hyperpolarization in rat mesenteric artery.

The effects of a series of symmetric tetra-n-alkylammonium (TAA) compounds with alkyl side chains of one to six carbons in length on acetylcholine-induced endothelium-dependent hyperpolarization were examined in rat mesenteric artery. All TAA compounds caused a concentration-dependent inhibition of the hyperpolarizing response to acetylcholine. The potency of TAAs showed a general trend to increase with the lengths of the alkyl side chains. The inhibitory effects of TAAs, excepting the smallest compound, on the acetylcholine response were reversible. However, TAAs with long alkyl side chains may act as antagonists at muscarinic receptors, because the suppressive effect on A23187-induced endothelium-dependent hyperpolarization was more marked with TAAs having smaller alkyl side chains. Conversely, the hyperpolarizing response to pinacidil, an ATP-sensitive K + channel opener, was significantly prevented only by TAA compounds with long alkyl side chains. TAA compounds with one- to three-carbon alkyl side chains caused a modest and reversible depolarization of the membrane, whereas the depolarizing effects of the compounds with four- to six-carbon alkyl side chains were marked and irreversible. These results suggest that TAAs could gain access to the target K + channels for endothelium-derived hyperpolarizing factor, the ATP-sensitive K + channels, and the K + channels responsible for the regulation of the resting membrane potential in different ways.