The effect of inhibitors of Na/H exchange and Na/Ca exchange on airway smooth muscle contractility.

We have previously shown that amiloride, an inhibitor of several cell membrane sodium exchangers and channels including Na/H exchange and Na/Ca exchange, inhibits receptor-operated contraction of bovine airway smooth muscle. However, the precise mechanism of action of amiloride is unknown. To evaluate the mechanism whereby amiloride reduces airway smooth muscle contractility, we compared the effects of amiloride with 5-N-methyl isobutyl amiloride and 5-N,N-hexamethylene amiloride, selective inhibitors of Na/H exchange, and 5-N(N-4-chlorobenzyl)-2,4-dimethyl benzamil, a selective inhibitor of Na/Ca exchange on histamine-induced contraction of bovine trachea. Unlike amiloride, none of the amiloride analogues, 5-N-methyl isobutyl amiloride (10 mumol/l), 5-N,N-hexamethylene amiloride (10 mumol/l) nor 5-N(N-4-chlorobenzyl)-2,4-dimethyl benzamil (20 mumol/l), inhibited histamine-induced contraction. Our results do not support the hypothesis that Na/H exchange or Na/Ca exchange are involved in histamine-induced contraction of airway smooth muscle.