Multiple mechanisms of reflex bronchospasm in guinea pigs

Abstract

The mechanisms of histamine- and bradykinin-induced reflex bronchospasm were determined in anesthetized guinea pigs. With intravenous administration, both autacoids evoked dose-dependent increases in tracheal cholinergic tone. Vagotomy or atropine prevented these tracheal reflexes. When delivered as an aerosol, bradykinin readily increased tracheal cholinergic tone, whereas histamine aerosols were much less effective at inducing tracheal reflexes. Also, unlike histamine, bradykinin could evoke profound increases in cholinergic tone without directly or indirectly (e.g., prostanoid dependent) inducing measurable airway smooth muscle contraction resulting in bronchospasm. Neither autacoid required de novo synthesis of prostanoids or nitric oxide to induce reflex tracheal contractions. Combined cyclooxygenase inhibition and tachykinin-receptor antagonism did, however, abolish all effects of bradykinin in the airways, whereas responses to histamine were unaffected by these pretreatments. The data indicate that histamine and bradykinin initiate reflex bronchospasm by differential activation of vagal afferent nerve subtypes. We speculate that selective activation of either airway C fibers or airway rapid adapting receptors can initiate reflex bronchospasm.

The rise of the phoenix: the expanding role of the eosinophil in health and disease

“…The AHR measured by inhalation of methacholine or histamine (PC20) involves sensory nerve stimulation of the smooth muscle via the vagus efferent nerves (36,37). In humans with AHR, these neural pathways are abnormally sensitive (38).…”

Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs

“…Reflex-mediated alterations in tracheal smooth muscle tone were monitored isometrically in the rostral extrathoracic trachea, as described previously (7,22). Pulmonary insufflation pressure was monitored with a pressure transducer attached to a side port of the tracheal cannula.…”

“…1) (9,22). Moreover, the trachea provides a convenient window on the activity of airway parasympathetic nerves throughout the airways (7,22,30). In the present study, we exploited these attributes to study interactions between airway afferent nerve subtypes on airway smooth muscle tone.…”

“…Myelinated airway mechanoreceptors, of which there are at least two types, are sporadically active throughout the respiratory cycle (4,36,39). Mechanoreceptors respond to the dynamic and/or sustained physical effects of lung inflation and deflation and may also be activated indirectly by bronchoconstrictors such as histamine, cysteinyl leukotrienes, or acetylcholine (4,7,11,38). The ongoing activity of these mechanoreceptors contributes to respiratory rhythm.…”

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

“…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.…”