Role of the parasympathetic nervous system and of cholinergic mechanisms in bronchial hyperreactivity.

The parasympathetic nervous system of the respiratory tract is involved in the control of airway calibre in three ways: through afferent nerve pathways (pulmonary reflexes); through efferent nerve pathways (reflexes, interaction between efferent vagus and mediators or modulating transmitter substances) and through cholinergic muscarinic receptors and postreceptor mechanisms in the target organ. To what extent do these mechanisms contribute to airway hyperreactivity? Pulmonary reflexes: Reflex bronchoconstriction has been established in divided lung experiments for histamine and in experiments involving an isolated segment of trachea for SO2. A reflex pathway is the most likely explanation for the heightened reactivity induced by aerosols of prostaglandin E2 and by maximal respiratory manoeuvers. Reflex bronchoconstriction is mediated through rapidly adapting ("irritant") receptors and through C-fibre endings. The influence of C-fibre endings is greater than hitherto suspected and many effects ascribed to irritant receptors are probably due to stimulation of C-fibre endings which outnumber myelinated fibres 3-4 to 1. From studies on the control of respiration (which reflect more directly the state of sensory receptors in the airways than studies of airway calibre) it appears that the activity of C-fibre endings increases during ozone-induced hyperreactivity. This could explain the increased bronchial reactivity seen in this condition. Interaction: Aerosols of serotonin cause bronchoconstriction when the vagus nerve is intact but have little effect during vagal block. This is an effect neither on afferent receptors nor on the end organ, but on the efferent nerve pathway. Interaction effects of this type ("cholinergic facilitation") are frequent and may be more important quantitatively than reflex effects. From data on serotonin and by analogy to other systems it appears that preganglionic and ganglionic sites are important points of interaction. Parasympathetic ganglia are located in the airway wall. Several transmitter substances have been identified in airway ganglia and in autonomic nerves, sensory and motor. Thus there seem to be convergent inputs capable of modulating transmission through the ganglia. An altered balance of converging ganglionic inputs may cause hyperreactivity. Receptors in airway smooth muscle may not be a homogeneous population. Muscarinic receptors are being classified into subgroups and the existence of at least 3 subtypes: M-1, M-2 and M-3 has been postulated. Their distribution depends on the tissue studied. They differ in agonist affinity messenger systems.(ABSTRACT TRUNCATED AT 400 WORDS)