Characterization of non‐adrenergic, non‐cholinergic inhibitory responses of the isolated guinea‐pig trachea: differences between pre‐ and post‐ganglionic nerve stimulation

Abstract

1 Di erences in the mechanism of non-adrenergic, non-cholinergic (NANC) inhibitory responses to preganglionic-and post-ganglionic nerve stimulation were investigated in the guinea-pig isolated trachea. 2 Stimulation of the vagus nerve at frequencies above 4 Hz elicited NANC relaxation of the trachealis muscle. Responses to low frequencies of stimulation (4 ± 8 Hz) were abolished by the nitric oxide (NO) synthase inhibitor L-NOARG (10 mM), while a L-NOARG resistant component was observed at higher stimulus frequencies. The L-NOARG-resistant component of NANC inhibitory responses to higher frequencies of vagus nerve stimulation were signi®cantly attenuated by the proteinase a-chymotrypsin (2 U/ml), suggesting that a neuropeptide such as VIP may contribute to NANC responses. 3 When postganglionic nerves were stimulated by electrical ®eld stimulation (EFS), responses were readily elicited at frequencies below 4 Hz. Like responses to vagus nerve stimulation, responses to low frequency (54 Hz) EFS were abolished by L-NOARG while a L-NOARG-resistant component was apparent at higher stimulus frequencies. 4 The L-NOARG-resistant component of NANC inhibitory responses to EFS was sensitive to achymotrypsin only if stimuli were delivered in either long trains at a low frequency (4 Hz for 10 ± 30 s) or short trains of high frequency (16 Hz for 2.5 ± 7.5 s). 5 Responses to preganglionic nerve stimulation were approximately 35% of the amplitude of responses to EFS in the same preparations. 6 In conclusion, responses to preganglionic and postganglionic NANC inhibitory nerve stimulation in the guinea-pig trachea di er in maximum amplitude, frequency-response characteristics and the contributions of cotransmitters. We suggest that these di erences may be explained by ®ltering of preganglionic input to postganglionic NANC neurons. These results have implications in all studies where EFS is considered to be representative of physiological stimulation of post-ganglionic nerve stimulation.

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

“…Although high voltage (10-20 V) efferent vagal stimulation has usually been associated with bronchoconstriction, we have shown that low voltage vagal stimulation can inhibit airway bronchoconstriction in addition to increasing HR and blood pressure. 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.…”

Characterization of the non‐nitrergic NANC relaxation responses in the rabbit vaginal wall

“…This suggested that a neuropeptide might mediate these responses since neuropeptides are known to be released following high frequency stimulation (Lundberg, 1996). Indeed, the peptidase α‐chymotrypsin has been shown to attenuate the responses in the guinea‐pig trachea (Moffatt et al ., 1999) and in the female pig urethra (Werkström et al ., 1997). In the current study non‐nitrergic NANC responses in the rabbit vaginal wall were inhibited with TTX and were greater in magnitude and duration at high frequencies, as in the pig urethra and guinea‐pig trachea, thus we hypothesized that they were mediated by a neuropeptide.…”

“…In this tissue high frequency stimulation (>12 Hz) elicited non‐nitrergic NANC relaxation responses (Werkström et al ., 1995). Similar responses have been reported in the guinea‐pig trachea (Moffatt et al ., 1999). This suggested that a neuropeptide might mediate these responses since neuropeptides are known to be released following high frequency stimulation (Lundberg, 1996).…”

“…EFS‐induced relaxations however were not affected by α‐chymotrypsin. It has previously been reported that α‐chymotrypsin is able to block non‐nitrergic EFS‐induced relaxations in the guinea‐pig trachea (Moffatt et al ., 1999) suggesting that the peptidase is capable of inhibiting responses to endogenously‐released neuropeptides as well as inhibiting responses to exogenously‐applied peptides. Since the peptidase had no effect on EFS‐induced relaxations in our experiments it is unlikely that any of these peptides are involved in the non‐nitrergic component of the NANC relaxation in the rabbit vaginal wall.…”

The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non‐adrenergic, non‐cholinergic relaxation responses of guinea‐pig pulmonary arteries

“…β ‐Adrenergic receptors contribute to pulmonary artery (PA) vasorelaxation by activation of pulmonary vascular smooth muscle adenylate cyclase (Fullerton, Hahn, Banerjee & Harken, 1994; Fullerton, Agrafojo & Mcintyre, 1996). In addition to β ‐adrenoceptor‐mediated responses, it is known that stimulation of the autonomic nerves to several organs causes responses which are neither adrenergic nor cholinergic (Gibson, Mirzazadeh, Hobbs & Moore, 1990; Postorino, Serio & Mule, 1995; Kubota, Hamasaki, Sata, Saga & Said, 1988; Moffatt, 1999; Gumusel, Orhan, Tolunay & Uma, 2001). One tissue in which such NANC relaxations have been identified is the guinea‐pig PA (Maggi et al.…”