title: Increased parasympathetic tone as the underlying cause of asthma: a hypothesis.
abstract: Asthma is a chronic inflammatory disease of airways that is characterized by increased responsiveness of the tracheo-bronchial tree to multiple number of stimuli. Immunological theory does not explain all features in asthma, for example hyper-reactivity of the airways. Neurogenic theory also fails to explain the pathogenesis of asthma comprehensively. Higher parasympathetic tone has been reported in asthmatics but has never been suggested as a major underlying cause of asthma. This article attempts to explain the occurrence of hyper-responsiveness, inflammatory/allergic reactions and broncho-constriction in asthma on a common basis of inherent higher parasympathetic tone in asthmatics. The higher background parasympathetic firing leads to increased nitric oxide (NO) production owing to its co-localization with acetylcholine (ACh) in inhibitory non-adrenergic and non-cholinergic (i-NANC) nerves. NO is a neurotransmitter of i-NANC system and it mediates bronchodilation. Increased NO release has been found to be responsible for hyper-responsiveness and increased inflammation in the airways. The authors suggest that an inherently higher background parasympathetic tone in concert with inflammation or a specific genetic background could modify the effects of NO on lung homeostasis in humans leading to increased susceptibility to an asthmatic state.
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi 110 029, India. drmanishgoyal@rediffmail.com
authors.forename: Manish
authors.initials: M
authors.lastname: Goyal
authors.forename: Harinder
authors.initials: H
authors.lastname: Jaseja
authors.forename: Narsingh
authors.initials: N
authors.lastname: Verma
mesh_terms: D000109:Acetylcholine / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001341:Autonomic Nervous System / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology; D018448:Models, Immunological; D009122:Muscle Hypertonia / Q000276:immunology; D018377:Neurotransmitter Agents / Q000276:immunology / Q000502:physiology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000276:immunology; D012137:Respiratory System / Q000276:immunology* / Q000294:innervation*; D014132:Trachea / Q000276:immunology
chemical_list: D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D000109:Acetylcholine