Central nervous system control of airway tone in guinea pigs: the role of histamine.
The central nervous system (CNS) plays an important role in the reflex control of bronchomotor tone, but the relevant neurotransmitters and neuromodulators have not been identified. In this study we have investigated the effect of histamine. Anesthetized male guinea pigs were prepared with a chronically implanted intracerebroventricular (icv) cannula and instrumented for the measurement of pulmonary resistance (RL), dynamic lung compliance (Cdyn), tidal volume (VT), respiratory rate (f), blood pressure (BP), and heart rate (HR). Administration of histamine (2-30 micrograms) icv caused a significant (P less than 0.05) reduction of Cdyn with no change in RL, VT, and f. At a dose of 100 micrograms icv, histamine caused an increase in RL (202 +/- 78%), a reduction of Cdyn (77 +/- 9%), an increase in f (181 +/- 64%), and a reduction of VT (53 +/- 18%). There were no changes in BP and HR after 100 micrograms of icv histamine. In contrast, intravenous administration of histamine (0.1-2 micrograms/kg) caused a dose-dependent decrease in Cdyn and increase in RL that was associated with tachypnea at each bronchoconstrictor dose. Intravenous histamine (2 micrograms/kg) produced a fall in BP and an increase in HR. The bronchoconstrictor responses to icv histamine were completely blocked by vagotomy and significantly reduced by atropine (0.1 mg/kg iv), whereas vagotomy and atropine did not block the bronchospasm due to intravenous histamine. Additional studies indicated that the pulmonary responses due to icv histamine (100 micrograms) were blocked by pretreatment with the H1-antagonist chlorpheniramine (1 and 10 micrograms, icv). These data indicate that histamine may serve a CNS neurotransmitter function in reflex bronchoconstriction in guinea pigs.
Mauser
P J
PJ
Department of Allergy and Inflammation, Schering-Plough Corporation, Bloomfield 07003.
Edelman
N H
NH
Chapman
R W
RW
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D001986:Bronchial Spasm / Q000209:etiology; D002744:Chlorpheniramine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007276:Injections, Intraventricular; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D018377:Neurotransmitter Agents; D011969:Receptors, Histamine H1 / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D018377:Neurotransmitter Agents; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D001285:Atropine; D006632:Histamine