Role of cholinergic, vagal reflexes on the bronchoconstrictor responses to histamine during carbon dioxide inhalation in conscious guinea-pigs.
Histamine-induced bronchoconstriction in conscious guinea-pigs involves a cholinergic, bronchoconstrictor reflex, but the role of this reflex during elevated levels of inspired carbon dioxide is unknown. In this study we examined the role of cholinergic, vagal reflexes on the bronchoconstrictor responses to histamine during CO2 inhalation. Guinea-pigs were placed inside a whole body plethysmograph for measurement of tidal volume (VT), respiratory rate (f) and minute volume (V) and a head chamber was used to deliver a hypercapnic gas mixture (10% CO2, 21% O2, 69% N2) and for inhalation of aerosolized drugs. Inhalation of CO2 caused an increase in VT, f and V and these effects were reduced by exposure to aerosolized histamine (0.01-0.05% for 30 s). The histamine-induced reduction of VT was significantly (P less than 0.05) attenuated following a 60 s exposure to inhaled atropine (0.03 and 0.1%) as was the reduction of VT due to inhaled methacholine. Intravenous atropine (1 mg/kg) also blocked the VT reduction due to aerosolized histamine. Intravenous administration of the ganglionic blockers hexamethonium (1 mg/kg) and mecamylamine (10 mg/kg) did not inhibit the histamine-induced reduction of VT at doses of these drugs that revealed systemic evidence of ganglionic blockade, i.e. inhibition of vagally stimulated bronchoconstriction and bradycardia. The results demonstrate that the bronchoconstrictor responses to histamine during CO2 inhalation in guinea-pigs involves stimulation of airway cholinergic receptors, but this response does not involve ganglionic neurotransmission. It is speculated that histamine's bronchoconstrictor effects during CO2 breathing involves stimulation of postganglionic, parasympathetic nerves innervating airway smooth muscle.
Chapman
R W
RW
Department of Allergy and Inflammation, Schering-Plough Corp., Bloomfield, NJ 07003.
Danko
G
G
D000336:Aerosols; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D002245:Carbon Dioxide / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008688:Methacholine Compounds / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D000336:Aerosols; D006584:Hexamethonium Compounds; D008688:Methacholine Compounds; D002245:Carbon Dioxide; D008464:Mecamylamine; D001285:Atropine; D006632:Histamine