Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

Lindén, Anders; Ullman, Anders; Skoogh, Bengt-Eric

doi:10.1111/j.1476-5381.1993.tb13652.x

Cited by 8 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it was not until 1988 that the first modern day vagus nerve stimulator was implanted into a patient for intractable epilepsy (30) and 1997 when the FDA approved the Cyberonics Inc.'s VNS Therapy (33). VNS using high voltages, however, is capable of inducing bronchoconstriction in human clinical settings (34) as well as in the animal models (18–24). In contrast, we have shown that the specific low voltage VNS signal applied in this guinea pig histamine model could reduce the Ppi.…”

Section: Discussionmentioning

confidence: 61%

“…The vagus nerve provides the dominant autonomic innervation of the airways and, through acetylcholine release from its pulmonary nerve endings, triggers bronchoconstriction by direct activation of muscarinic acetylcholine receptors on airway smooth muscle cells (17). Vagus nerve stimulation (VNS) is an important tool for investigating the neural pathways and receptors that control airway smooth muscle tone and when stimulated with relatively high voltages (10–20 V) has been shown to increase bronchoconstriction in a variety of species including guinea pigs (18–20), dogs (21), cats (22), swine (23), and rabbits (24). We have selected the guinea pig animal model for investigating histamine and VNS since it is the more established animal model and has been well validated over the past 25 years for assessments of airway tone (25–28).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Hoffmann¹,

Mendez²,

Staats

et al. 2009

Neuromodulation: Technology at the Neural Interface

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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

Hoffmann¹,

Mendez²,

Staats

et al. 2009

Neuromodulation: Technology at the Neural Interface

View full text Add to dashboard Cite

“…However, high concentrations of L‐NOARG failed to alter adult bronchial relaxations to EFS at any of these. In order to compare responses across ages, we precontracted tissues to 50% of the ACh E max , as it has been previously found that the level of muscle tone may influence the size of nerve‐induced inhibitory relaxations and hence the release of NO (Cohen & Berkowitz, 1974; Vargas et al , 1990; Linden et al , 1993).…”

Section: Discussionmentioning

confidence: 99%

Transition of functional innervation in the developing porcine airway from nitrergic to catecholaminergic

Connellan

Mitchell

1998

British J Pharmacology

View full text Add to dashboard Cite

1 We determined the distribution and chemical nature of the inhibitory neurotransmitter(s) to the airway smooth muscle (ASM) before and after birth. 2 Relaxation responses to electrical ®eld stimulation (EFS) were studied in isovolumic bronchial segments from foetal (approximately 100/115 days gestation) and adult (25 kg) pigs, and in isovolumic tracheal segments from the foetus, and tracheal smooth muscle strips from the adult pig. Preparations were conditioned in low doses of atropine (10 77 M) to reduce the eects of excitatory neurotransmission and then exposed to carbachol to produce submaximal muscle tone. Some studies were also carried out on bronchial segments from 4 week old pigs. 3 EFS (65 V, 2 ms, 5 ± 20 Hz for 5 s) produced a TTX-sensitive relaxation in epithelium-intact and epithelium-denuded preparations. In foetal bronchial and tracheal preparations, EFS-induced relaxation was strongly inhibited by N G -nitro-L-arginine (L-NOARG, 10 76 to 10 74 M; P50.01 ± 0.001). However, in the adult, only relaxations of the trachea were inhibited by L-NOARG; bronchi were resistant to L-NOARG and also to N-nitro-L-arginine methyl ester (L-NAME, 5 The onset of relaxation to EFS was more prompt and the rate of relaxation more rapid in foetal bronchi than in adult bronchi (P50.0005). Maximum relaxation and recovery times were the same. 6 Foetal and adult bronchi were relaxed by sodium nitroprusside (SNP) with similar sensitivity and maximum eect. The rate of relaxation to SNP was not dierent in the two ages. 7 In the absence of atropine and carbachol, excitatory cholinergic responses to EFS (65 V, 2 ms, 5 Hz for 20 s) were not altered by L-NOARG (10 74 M) or L-NAME (10 74 M) in the adult bronchus but were modestly increased by L-NOARG in the foetal bronchus (P50.01). 8 The tracheobronchial tree appears functionally innervated by nitrergic input to the smooth muscle before birth. However, at or after 4 weeks of age the inhibitory neural input to the bronchi is catecholaminergic, but it remains nitrergic in the trachea. There is also a weak nitrergic pre-or postsynaptic inhibition of the eects of cholinergic neurotransmission in the foetal bronchus but not in the adult.

show abstract

“…We could further demonstrate in our study that all nerve-mediated relaxation was blocked by TTX (9). NOreleasing inhibitory nonadrenergic, noncholinergic (iNANC) fibers have repeatedly been shown to be TTX sensitive (10), suggesting that our use of TTX was sufficient to evaluate and discount the possible contribution of NO-mediated neuronal relaxation, the mechanism proposed by Drake and colleagues.…”

mentioning

confidence: 52%

The bronchodilatory capacity of imiquimod: the existence of two mechanisms

Larsson

Manson

Starkhammar

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

TO THE EDITOR: We recently published a study investigating the bronchodilatory capacity of the Toll-like receptor 7 (TLR7) agonist imiquimod, establishing the presence of a nonneuronal, TLR7-independent mechanism of dilation (9). Our study adds new information to the previously published reports, which demonstrated that relaxation can be mediated by a TLR7-dependent release of nitric oxide (NO) from innervating nerves (2, 5). In a Letter to the Editor, Drake (2a) now argues that the data we report do not provide sufficient evidence to support our conclusion of a nonneuronal TLR7-independent mechanism. We would instead argue that our results are sound and reflect the presence of an additional mechanism for imiquimod-mediated bronchodilation.In our study, we demonstrated that administration of the neurotoxin tetrodotoxin (TTX) in vitro had no effect on imiquimod-induced bronchodilation and thus concluded that neuronal pathways were not involved in dilation (9). Due to the presence of TTX-resistant nerves, particularly those originating from the nodose ganglia (8), Drake suggests that this is not sufficient to discount neuronal involvement. However, the contribution of TTX-resistant nodose-derived sensory nerves to relaxation is unlikely. Although these nerves contain relaxatory mediators, namely pituitary adenylate cyclase-activating polypeptide (PACAP) (1, 3) and substance P (SP) (4, 12), SP induces relaxation via the epithelium (4) and PACAP relaxes independently of nitric oxide synthase (NOS) (7). This argues against Drake's proposed mechanism of epithelium-independent and NO-mediated relaxation. In addition, activation of sensory neurons by imiquimod has been shown to be TLR7 independent (6), which suggests that a TLR7-dependent neuronal mechanism of relaxation does not occur via sensory neurons. We could further demonstrate in our study that all nerve-mediated relaxation was blocked by TTX (9). NOreleasing inhibitory nonadrenergic, noncholinergic (iNANC) fibers have repeatedly been shown to be TTX sensitive (10), suggesting that our use of TTX was sufficient to evaluate and discount the possible contribution of NO-mediated neuronal relaxation, the mechanism proposed by Drake and colleagues.Noticeably, there are discrepancies between our results and those published previously by Drake and colleagues, particularly from experiments assessing the roles of TLR7 and NO, using the interventions IRS661 and N G -nitro-L-arginine methyl ester (L-NAME)/N G -monomethyl-L-arginine (L-NMMA), respectively. Using the same concentration of IRS661 as previously used in vitro (5), we were unable to see any effect on imiquimod-induced bronchodilation. Although we did not confirm the ability for IRS661 to inhibit TLR7 in this study, we have previously confirmed its ability to inhibit TLR7-mediated responses in isolated airway smooth muscle cells (11). In addition, we showed that the TLR7 agonist CL264 failed to induce relaxation or inhibit histamine-induced Ca 2ϩ flux, which would dispute a role for TLR7. The discrepancy between ...

show abstract

Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

Cited by 8 publications

References 33 publications

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

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

Transition of functional innervation in the developing porcine airway from nitrergic to catecholaminergic

The bronchodilatory capacity of imiquimod: the existence of two mechanisms

Contact Info

Product

Resources

About