Bronchopulmonary effects of clonidine on the bronchomotor responses of the guinea-pig.

In conscious guinea pigs, clonidine (10 and 100 micrograms/kg i.v.) lowered diastolic (-7.9 +/- 3.5 and -12.4 +/- 5.2%) and systolic (-8.6 +/- 3.0 and -11.9 +/- 4.2%) arterial pressure and reduced heart rate (-14.5 +/- 3.9 and -27.7 +/- 3.8%), but did not significantly modify pulmonary airway resistance. Hypotension was suppressed by yohimbine and bradycardia was partially suppressed by atropine and yohimbine, which demonstrates in this animal an alpha 2-adrenergic effect for hypotension and a mixed cholinergic and alpha 2-adrenergic effect for bradycardia. Clonidine (10 and 100 micrograms/kg i.v.) enhanced the bronchoconstrictor effects of histamine 20 micrograms/kg (+80.0 +/- 22.5 and 89.1 +/- 26.5%), acetylcholine 25 micrograms/kg (+66.4 +/- 19.8 and +95.4 +/- 25.4%) and serotonin 15 micrograms/kg (+68.5 +/- 23.2 and +81.4 +/- 34.1%). The duration of this effect was comparable to that of the hypotensive and cardiac effects of clonidine. The effects of clonidine were suppressed after pretreatment with propranolol, reserpine or pentobarbitone, all drugs which enhance the bronchoconstrictor effect of ACh. Yohimbine (1 mg/kg), piperoxan (0.3 mg/kg) or prazosin in high dosage (0.3 mg/kg) inhibited the potentiation by clonidine of ACh-induced bronchoconstriction, whereas prazosin in lower doses (0.03 mg/kg) or AR-C 239 (0.05 mg/kg) had no action. A specific involvement of alpha 2-adrenoceptors stimulated by clonidine with subsequent reduction of the adrenergic activity associated with bronchospasm could therefore be demonstrated in the conscious guinea-pig during bronchomotor reactions.