Age-related Changes in Airway Responsiveness to Phosphodiesterase Inhibitors and Activators of Adenyl Cyclase and Guanylyl Cyclase

Abstract The influence of animal age on the responsiveness of guinea-pig and rat isolated tracheal smooth muscle to the non-selective inhibitors of phosphodiesterase, theophylline and papaverine and to the adenylyl cyclase and soluble guanylyl cyclase activators, forskolin and sodium nitroprusside respectively, was examined. Significant age-related decreases in the potencies of theophylline and papaverine were observed across the age ranges in guinea-pig (2.8- and 3.4-fold decreases respectively) and rat (1.9- and 2.6-fold decreases respectively) trachea, suggesting age-related falls in the activity of phosphodiesterase in these tissues. However, maximum relaxant responses (E max ) to these agents were not altered with increasing animal age. The relaxant potency of sodium nitroprusside also decreased 4.4-fold across the age range in guinea-pig isolated trachea but not in rat isolated tracheal tissue, suggesting age-related falls in soluble guanylyl cyclase activity in guinea-pig trachea. In contrast, neither forskolin potency nor E max changed significantly with increasing age in either guinea-pig or rat tracheal tissue. The present data indicate that ageing in both guinea-pigs and rats was associated with decreased relaxant potency of phosphodiesterase (PDE) inhibitors rather than to changes in adenylyl cyclase activity although reduced soluble guanylyl cyclase activity was also detected in the guinea-pig.