Abstract
The effects of brovanexine (BvX) and BR-227 on sectetory activities of tracheal submucosal glands (SG) including behavior of mucus glycoproteins in the cells were investigated. BvX, BR-227 or bromhexine (BH) was given repeatedly at a dose of 10 or 20 mg/kg p.o. a day, to rats for 1, 3, 7 or 14 days. Then, the trachea was excised and drug effects were determined according to our histological/histochemical technique. The outer diameter of the acini of SG did not change, but the inner diameter markedly increased by the drug given for 3-14 days. The ratio of the acinar inner diameter to the tracheal wall thickness (AIWR) was increased with the 3, 7, and 14 day treatments with BvX or BR-227 at a dose of 10 mg/kg a day. On the other hand, these drugs at a dose of 20 mg/kg a day caused an increase in AIWR when drug was given for 1-14 days. BH (10 mg/kg a day)-induced increase in AIWR was shown when drug was administered for 7 and 14 days. The number of SG cells stained blue with alcian blue (pH 2.5)/periodic acid-Schiff decreased with the 1, 3, 7 and 14 day treatments, and a part of SG cells became red with the 7 and 14-day treatments. There was no significant difference in the effects among the three drugs both qualitatively and quantitatively. These findings indicate that repeated treatments with BvX and BR-227 have an effective secretagogic action on SG, and in addition, a mucolytic action toward acid glycoprotein in granules of the cells. The onset of mucolytic action of any of these drugs seemed to be ahead of that of the secretagogic action.