SENSITIVITY AND RESPONSIVENESS OF TRACHEAL AND BRONCHIAL TISSUES FROM YOUNG AND OLD GUINEA-PIGS - EFFECT OF CALCIUM-ANTAGONISTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (3) , 612-619
Abstract
BaCl2 contracted tracheas and bronchi from young and old guinea pigs and equipotent in all tissues. Efficacies were significantly greater in tracheal vs. bronchial tissues within and between age groups. The effects of nitrendipine and verapamil were completely reversible with washing in tissues from young animals; in tissues from old animals the effects of the antagonists were irreversible. Nitrendipine (10, 50 and 100 nM) reduced the efficacy of BaCl2 in tissues from old animals from 0-70%, depending on the tissue source and the concentration of Ca channel blocker used. Verapamil (1-10 .mu.M) reduced the contractile response of tracheal tissues from old animals to Ba by 50% at the maximally effective concentration of the agonist. In tissues from young animals, nitrendipine (50-100 nM) totally abolished the response to Ba whereas 10 nM reduced efficacy by 80% without affecting tissue sensitivity. Verapamil (1 .mu.M) reduced responses in tracheal and bronchial tissues from young animals by .apprx. 60%. In preparations incubated with polyethylene glycol 400 (vehicle for nitrendipine, 1 .mu.g/ml final bath concentration), neither efficacy nor potency of BaCl2 was altered in tracheal or bronchial tissues from young animals; in bronchial and tracheal tissues from old animals, efficacy was slightly increased. Indomethacin pretreatment abolished the effects of polyethylene glycol incubation. Carbachol- and histamine-induced contractions of tracheal and bronchial tissues from young and old guinea pigs were unaffected by nitrendipine. These agents require Ca for contraction. Contractile responses are rapidly lost in all tissues placed in a Ca-free medium. Indomethacin does not reduce the effects of nitrendipine even though its own activity is to increase the efficacy of Ba. The relaxant activities of isoproterenol and aminophylline are unaltered by nitrendipine treatment of the tissues. Whereas Ba-induced tension is reversed by nitrendipine and verapamil, histamine- and carbachol-induced tone are essentially unaffected. The following is concluded: Ca channel blockers inhibit Ba-induced contraction of guinea pig respiratory tissues; entry of Ca via voltage-dependent Ca channels does not significantly contribute to basal airway tone; the effects of Ca channel blockers are reduced during development; and tension development and reduction by a spectrum of agonists is independent of entry of Ca via the voltage-dependent channel in guinea-pig airway muscle.