The Role of Vagal Reflex in Mechanism of Secretagogic Action of Bromhexine

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Abstract
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 h after administration, and the 2nd prolonged increase occurred during 2-6 h after administration. The early stimulant phase was almost abolished by atropine, 1 mg/kg i.v. or bilateral cervical vagotomy; the 2nd stimulant phase was not affected by these treatments. Emetine induced a similar early increase in AIWR at 0.5 h after administration, the change also being abolished by atropine or surgical vagotomy. The number of submucosal glandular cells 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 stained red markedly increased. These histochemical changes in glandular cells were not influenced by atropine or surgical vagotomy treatment. Bromhexine exerts a secretagogic action on submucosal glands and a mucolytic action toward acid glycoproteins inside the cells in vivo. The secretagogic action of bromhexine occurs biphasically; the 1st phase results from the vagal reflex probably through a gastrointestinal irritation, and the 2nd phase results from a direct action on the glands.