Nitric oxide as a neurotransmitter in human airways.
Human airway smooth muscle possesses a prominent nonadrenergic noncholinergic (i-NANC) bronchodilator response. Nitric oxide (NO) appears to account for all the i-NANC response in human central and peripheral airways in vitro. Furthermore, it appears that i-NANC relaxations in human trachea are associated with a concomitant selective elevation of cGMP, but not cAMP levels, which are inhibited by an NO synthase (NOS) inhibitor. This confirms the hypothesis that the L-arginine/NO/cGMP pathway is responsible for mediating the i-NANC response in this tissue. It is not certain from where the NO is formed or the location of the NOS enzyme. However, in human trachea, NOS immunoreactivity (NOS-IR) has been described in nerve fibres originating from intrinsic neurons. In addition, the density of NOS-IR is reduced from proximal to distal airways and this correlates with functional data describing a reduced i-NANC relaxation response from central to peripheral airways. The i-NANC bronchodilator nerves are the only neural relaxant pathway in human airways and, therefore, it is important to determine whether there is any defect in the ability of these nerves to function in diseased airways. In fact, functional and immunohistochemical data suggest that there may be a deficiency in NOS-IR nerves leading to a decreased i-NANC response in tissue from patients with cystic fibrosis. NOS inhibitors appear to enhance the cholinergic bronchoconstriction in human airways in vitro. Therefore, if the nitrergic innervation is dysfunctional in inflammatory conditions, its absence may lead to exaggerated bronchoconstriction.
Belvisi
M G
MG
Department of Thoracic Medicine, National Heart and Lung Institute, Chelsea, London, U.K.
Ward
J K
JK
Mitchell
J A
JA
Barnes
P J
PJ
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016084:Bronchoconstriction / Q000502:physiology; D001993:Bronchodilator Agents / Q000494:pharmacology; D006801:Humans; D009130:Muscle, Smooth / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012119:Respiration / Q000187:drug effects / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects
D001993:Bronchodilator Agents; D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester