The effect of Ca2+ channel modulators on vagally induced bronchoconstriction in the guinea-pig.

The effects of N- and L-type voltage operated calcium channel (VOCC) antagonists were examined on the bronchoconstriction induced by vagal stimulation in artificially respired guinea-pigs. Vagal stimulation produced a reproducible and consistent bronchoconstrictor response which corresponded to an increase in pulmonary inflation pressure equivalent to (10.4 +/- 1.0%) of the maximum. This vagally induced rise in pulmonary inflation pressure was reduced (54% P less than 0.001) by pretreatment with atropine (1 mg/kg i.v.) and almost completely blocked by pretreatment with capsaicin (54.5 mg/kg s.c.) and atropine. omega-Conotoxin GVIA (CgTx) (5-20 micrograms/kg i.v.) caused a dose and time-related inhibition of the vagal response but did not affect either methacholine or substance P (SP)-induced bronchoconstriction. Combination studies with CgTx, atropine and capsaicin pretreatment revealed that CgTx effectively blocked both the atropine-sensitive cholinergic component and the capsaicin-sensitive non-adrenergic non-cholinergic (NANC) component of the vagal response. Selective L-type VOCC antagonists nicardipine, diltiazem and verapamil, at doses which had significant cardiovascular effects, did not reduce the rise in pulmonary inflation pressure to vagal stimulation. This study indicates that N-type VOCCs are important in controlling the release of neurotransmitters from both the cholinergic and NANC neurones within the airways of guinea-pigs.