The role of vagal reflex in mechanism of secretagogic action of bromhexine.

The in vivo effect of bromhexine on secretory activities of tracheal submucosal glands was investigated with a histological/histochemical technique with reference to a role of the vagal reflex. When bromhexine was given at 5, 10 or 20 mg/kg into the stomach of anesthetized dogs, the ratio of acinar inner diameter of the submucosal gland to wall thickness (AIWR) markedly increased in a biphasic manner; the early transient increase was seen 0.5 hr after administration, and the second prolonged increased occurred during 2 to 6 hr after administration. The early stimulant phase was almost abolished by atropine, 1 mg/kg i.v., or bilateral cervical vagotomy, whereas the second stimulant phase was not affected by these treatments. Emetine also induced a similar early increase in AIWR at 0.5 hr after administration, the change also being abolished by atropine or surgical vagotomy in this case. The number of submucosal glandular cells which stained blue and purple with a combination of alcian blue at pH 2.5 and periodic acid-Schiff was decreased by bromhexine, but the cell number which stained red was markedly increased. These histochemical changes in glandular cells were not influenced by treatment with atropine or surgical vagotomy. In the present study, it was found that bromhexine exerts both a secretagogic action on submucosal glands and a mucolytic action toward acid glycoproteins inside the cells in vivo. Also, the secretagogic action of bromhexine occurs biphasically; the first phase results from the vagal reflex probably through a gastrointestinal irritation, and the second phase results from a direct action on the glands.