The effects of histamine, acetylcholine and 5‐hydroxytryptamine on lung mechanics and irritant receptors in the dog.

Abstract

SUIMMARY1. The ability of histamine, acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) given i.v. and by aerosol to induce reflex bronchoconstriction and to activate lung irritant receptors has been studied in dogs anaesthetized with chloralose. 4. Histamine, 5-HT and ACh given by aerosol and i.v. increased lung irritant receptor discharge. Irrespective of the route of administration, for a given change in RL histamine produced a greater increase in irritant receptor discharge than did ACh or 5-HT, which produced similar increases.5. For a given change in RL, histamine, ACh and 5-HT were more effective in activating lung irritant receptors when given I.v. than by aerosol.6. The mechanisms of irritant receptor activation by histamine, ACh and 5-HT and the relationship between irritant receptor discharge and reflex bronchoconstriction are discussed.

The Action of Sodium Cromoglycate on ‘C’ Fibre Endings in the Dog Lung

“…The chest was opened along the mid-line and the vagi were cut at the level of the diaphragm. The cervical vagosympathetic nerves were divided and impulses were recorded, using conventional electrophysiological equipment (Dixon, Jackson & Richards 1979), from fine strands (containing one or two actual fibres) teased from the distal end of the left cervical vagus. Lung 'C' fibre endings were identified by their sparse 0007-1 188/80/090011-03 $01.00 and irregular pattern of discharge, by their response to hyperinflation (3 to 4 tidal volumes) and capsaicin (10 j.g/kg i.v.…”

The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats

“…*P Ͻ 0.05 vs. corresponding baseline value. these two types of lung sensory receptors by mechanical stimuli, such as an increase in interstitial fluid volume (15,36) and changes in lung mechanics (8,11,19,20), has been reported. Furthermore, ⅐OH and cyclooxygenase metabolites may cause pulmonary edema (13,26).…”

“…Both ⅐OH and cyclooxygenase metabolites, either administered exogenously (2,10,20,28,38,39) or formed endogenously (6,7,8,22,23), can chemically or mechanically stimulate lung C fibers and RARs in several species. On the other hand, endotoxin produces an increase in total lung resistance (RL) and a decrease in dynamic lung compliance (Cdyn) (21,43,44), both of which are potential mechanical stimuli for RARs (11,19). The role of ⅐OH, cyclooxygenase metabolites, and changes in lung mechanics in the endotoxin-induced stimulation of these two types of lung sensory receptors remain to be investigated.…”

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

“…In regard to the nerves, many studies have shown synergistic interactions between spasmogens and electrical stimulation of the vagal nerves (17,33,57,88,114,137,217,258). Similarly, a decrease in responsiveness to spasmogens (other than ACh (88)) was observed following vagotomy (59,137,157,258), cooling of the vagal nerves (58,88), or treatments with either atropine (59,219), tetrodotoxin (219) or hexamethonium (59). These results suggest that the basal cholinergic tone synergistically interacts with the exogenously delivered spasmogen.…”

“…These results suggest that the basal cholinergic tone synergistically interacts with the exogenously delivered spasmogen. These studies are not included in Table 1 because it is not clear whether the potentiating effect is due to a true synergistic effect at the level of ASM-force generation or due to the ability of the spasmogens to either trigger a vagal reflex (36,58,74,157) or to increase cholinergic neurotransmission and/or synaptic transmission at the ganglia (217). These latter phenomena would lead to more ACh release and concomitantly higher ASM activation for the same neural input.…”