Age-related changes in guinea pig respiratory tissues: considerations for assessment of bronchodilators.

Tracheal tissues from immature guinea pigs were significantly more sensitive to histamine and carbachol than their counterparts from mature animals. Bronchial but not tracheal tissues from immature animals were more sensitive to isoproterenol and salbutamol than tissues from mature animals. Functional antagonism between carbachol-induced tension and salbutamol-induced relaxation was greatest in bronchial tissues from immature animals. Functional antagonism was not evident when a concentration of histamine required to induce maximal but not supramaximal tension was used to induce tone. Inhibition of catechol-o-methyl transferase (COMT) with U 0521 (10 microM) or inhibition of extraneuronal uptake with hydrocortisone (200 microM), in tissues from animals in either age group, affected neither the potency of, nor the extent of relaxation induced by, isoproternol or salbutamol in histamine-contracted tissues. We conclude that extraneuronal uptake and metabolism by COMT do not modify tissue sensitivity to the relaxants studied. Therefore age-related changes in the relaxant properties of isoproterenol and salbutamol are not due to differences in their uptake or metabolism but probably reflect changes at the receptor level.