Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs

Abstract

Nitric oxide (NO), which can be derived from the nervous system or the epithelium of the airway, may modulate airway responsiveness. We investigated how NO derived from the airway nervous system would affect the airway responsiveness to histamine and acetylcholine in mechanically ventilated guinea pigs. An NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mmol/kg i.p.) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomer D-NAME (1 mmol/kg i.p.), in contrast, had no effect. The L-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg i.v.) and atropine (1 mg/kg i.v.). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg i.v.) completely abolished enhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter the L-NAME-induced airway hyperresponsiveness, whereas sympathetic stellatectomy completely abolished it. Results suggest that NO that was presumably derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs.

Inhibition of Histamine-Induced Bronchoconstriction in Guinea Pig and Swine by Pulsed Electrical Vagus Nerve Stimulation

“…In human tetraplegic patients, but not low paraplegics, there is reduced baseline airway caliber suggesting that sympathetic interruption could be responsible for the heightened vagomotor airway tone (50). Thus, while these examples support a possible contribution by the SNS, they do not contradict the role of the iNANC system as the principal bronchodilating neural pathway (35) since sympathetic nerves have also been shown to include iNANC fibers (47), the iNANC system is widely distributed in the human airways from the middle trachea to the distal bronchi, and it has been shown to relax cholinergic‐induced contractions (7).…”

“…The mechanism is unclear, but in isolated guinea pig trachea, efferent VNS‐induced NANC inhibition (46) was frequency dependent with the maximal inhibition at 32 Hz and similar to our signal. Alternatively, the afferent vagal nerve has been linked with activation of the SNS with either adrenergic nerve (42) or iNANC nerves (47) mediating relaxation in response to histamine. Although the role of smooth muscle SNS innervation on human bronchomotor tone is in question, SNS has been demonstrated in the lungs of most vertebrate species and is known to innervate the human lung such as the pulmonary vasculature (48).…”

Reflex regulation of airway sympathetic nerves in guinea‐pigs

“…Innervation of the intrathoracic airways is primarily derived from the thoracic sympathetic ganglia. Immunohistochemical analyses and circumstantial evidence gathered in functional studies suggests that a subpopulation of the postganglionic thoracic sympathetic nerves innervating the airways are non‐adrenergic, utilizing the peptide vasoactive intestinal peptide (VIP and related peptides) and/or the gaseous transmitter nitric oxide (NO, synthesized from arginine by the neuronal isoform of NO synthase) to relax airway smooth muscle (Bowden & Gibbins, 1992; Fischer et al 1996; Matsumoto et al 1997). In our pharmacological analyses, we found little evidence for a prominent non‐adrenergic component of the sympathetic response in the trachea, as propranolol reduced the nerve‐mediated relaxations (evoked electrically or reflexively) by an average of >95%.…”

NADPH-diaphorase histochemistry reveals an autonomic-like innervation in the postnatal hamster cochlea

“…Studies applying NOS inhibitors have demonstrated a significant decrease in cochlear blood flow following inhibitor application (Brechtelsbauer et al, 1994). Recent evidence indicates that NOS and NADPH-diaphorase are present in a subset of postganglionic sympathetic fibers in locations throughout the body (Fischer et al, 1996;Davisson et al, 1997;Matsumoto et al, 1997;Vials et al, 1997). Thus, the sympathetic innervation of the cochlea may act as one source of NO that mediates blood flow and vascular tone during early stages of the cochlear development.…”