Evidence that part of the NANC relaxant response of guinea‐pig trachea to electrical field stimulation is mediated by nitric oxide

Li, Chun Guang; Rand, M. J.

doi:10.1111/j.1476-5381.1991.tb12137.x

Cited by 288 publications

(160 citation statements)

References 16 publications

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“…Discussion NO-synthase inhibitors have been shown to block NANC relaxations in the mouse anococcygeus , guinea-pig trachea (Tucker et al, 1990;Hobbs et al, 1991;Li & Rand, 1991) and rat gastric fundus (Li & Rand, 1990;Boeckxstaens et al, 1991); the inhibition is stereoselective and is reversed by L-, but not D-, arginine. Further, in the anococcygeus the relaxations to both NANC stimulation and nitrovasodilators are selectively reduced by the guanylate cyclase inhibitor N-methylhydroxylamine (Gibson & Mirzazadeh, 1989b).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, drugs known to inhibit EDRF synthesis, such as L-NG-monomethyl-arginine (Moncada et al, 1989) and L-N0-nitro-arginine (L-NOARG; Moore et al, 1990), reduce NANC relaxations in a variety of tissues, including the anococcygeus Ramagopal & Leighton, 1989;Gibson et al, 1990;, trachea (Tucker et al, 1990;Li & Rand, 1991), blood vessels (Toda & Okamura, 1990), gastrointestinal tract Boeckxstaens et al, 1990;Li & Rand, 1990), and urogenital tract (Gillespie, 1990;Ignarro et al, 1990a;Andersson et al, 1991;Holmquist et al, 1991). In addition, Larginine:nitric oxide (NO) synthase, the enzyme involved in the generation of EDRF, has been detected by immunocytochemistry in nerve terminals in both the central and peripheral nervous systems (Bredt et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…However, its effects on NANC responses have been less widely studied and results have been varied; Gillespie & Sheng (1990) found that hydroquinone produced a small reduction of NANC relaxations of the rat anococcygeus but had no effect on the bovine retractor penis. The object of the present study was to investigate in more detail the interaction between hydroquinone and NANC nerves by determining its effects on three other tissues possessing an endogenous nitrate NANC system: the mouse anococcygeus , guinea-pig trachea (Tucker et al, 1990;Li & Rand, 1991), and the rat gastric fundus (Li & Rand, 1990). In addition, an attempt was made to determine whether the effect of hydroquinone resulted from production of superoxide anions.…”

Section: Introductionmentioning

confidence: 99%

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Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non‐vascular smooth muscle: role of superoxide anions

Hobbs

Tucker

Gibson

1991

British J Pharmacology

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1 The influence of hydroquinone on relaxations induced by nitric oxide (NO), nitrovasodilator drugs, and non-adrenergic, non-cholinergic (NANC) field stimulation has been investigated in three tissues in which endogenous nitrates have been implicated in the NANC response; the mechanism of action of hydroquinone was also studied. 2 In mouse anococcygeus, hydroquinone (10-1OOpM) produced a concentration-dependent inhibition of relaxations induced by 1S5UM NO. Hydroquinone, 100pMm, which reduced responses to NO by 85%, had no effect on relaxations induced by NANC field stimulation (1OHz; 20s trains), hydroxylamine (1OpM), sodium nitroprusside (1 gM) or sodium azide (20juM).3 In guinea-pig trachea, 100pM hydroquinone reduced relaxations to 150pM NO by 75%, but had no effect on those to NANC stimulation (1OHz; 30s trains) or sodium azide (5 pM).4 In rat gastric fundus, 100pUM hydroquinone reduced relaxations to 1 ,M NO by 85%, but had no effect on those to NANC stimulation (0.5 Hz; 15 s trains) or sodium azide (2pM). 5 Superoxide dismutase (SOD; 50uml-1) had no effect on relaxations of the mouse anococcygeus in response to 15,UM NO or 10Hz NANC stimulation. Further, the inhibition of responses to NO by hydroquinone was unaffected in the presence of SOD. 6 Hydroquinone (10-1OOuM) failed to generate superoxide anions, as detected by a chemiluminescent assay. However, 100piM hydroquinone, like SOD (50uml-1), produced almost complete inhibition of superoxide anion chemiluminescence induced by xanthine (500pgM): xanthine oxidase (0.07 u ml-1). 7 It is concluded that, in our system, hydroquinone inhibits NO by acting as a free radical scavenger rather than by generating superoxide anions. The ability of hydroquinone to block relaxations to NO, but not NANC stimulation, may suggest that the endogenous nitrate substance released by these NANC nerves may not be free NO, but may be an NO-containing, or NO-generating, molecule.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non‐vascular smooth muscle: role of superoxide anions

Hobbs

Tucker

Gibson

1991

British J Pharmacology

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“…The primary functional relaxant innervation in both species is parasympathetic and noncholinergic in nature. VIP (and related peptides) and the gaseous transmitter nitric oxide (NO, synthesized from arginine by the the neuronal isoform of NO synthase) have been implicated in nonadrenergic-noncholinergic nerve-mediated relaxations of human and guinea pig airway smooth muscle [35,[75][76][77][78]. VIP and NO synthase have both been identified in the airway parasympathetic nerves of human and guinea pig airways.…”

Section: Introductionmentioning

confidence: 99%

Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

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The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed.

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“…In the guinea-pig trachea, nitric oxide is one of the transmitters which mediate non-adrenergic, non-cholinergic (NANC) relaxations (Tucker et al, 1990;Belvisi et al, 1991;Li & Rand, 1991). Although NANC innervation exists in the airways of many species such as rats, rabbits, cats, cows, horses, monkeys and man, it has not been described in the airways of the dog (Diamond & Altiere, 1988).…”

Section: Isometric Tensionmentioning

confidence: 99%

Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide‐like substance

Gao

Vanhoutte

1993

British J Pharmacology

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1 The involvement was assessed of an endogenous nitric oxide-like substance in contractions of canine bronchi to acetylcholine. 2 Canine third order bronchial rings, in some of which the epithelium was removed mechanically, were suspended in organ chambers and isometric tension was recorded. In some experiments, the content of guanosine 3',5'-cyclic monophosphate (cyclic GMP) of the bronchi was also measured. 3 Acetylcholine induced concentration-dependent contractions. The contractions were potentiated by nitro-L-arginine (an inhibitor of the synthesis of nitric oxide), oxyhaemoglobin (a scavenger of nitric oxide), and methylene blue (an inhibitor of soluble guanylate cyclase). The magnitude of the potentiation to acetylcholine-induced contractions by these inhibitors were not significantly different between tissues with and without epithelium. 4 Acetylcholine induced a concentration-dependent increase in intracellular content of cyclic GMP, which was similar in bronchi with and without epithelium. These increases were abolished by nitro-Larginine and methylene blue. 5 During contractions to acetylcholine, exogenous nitric oxide relaxed the canine bronchi. The relaxations were not affeced by nitro-L-arginine, but were augmented by superoxide dismutase plus catalase, and were abolished by methylene blue. 6 These observations suggest that, during contraction evoked by acetylcholine, the production of an endogenous nitric oxide-like substance increases and in turn attenuates the response of the airways to the muscarinic agonist. However, the endogenous nitric oxide-like substance does not play a major role in the epithelium-dependent attenuation of the contraction to acetylcholine in canine bronchi.

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Evidence that part of the NANC relaxant response of guinea‐pig trachea to electrical field stimulation is mediated by nitric oxide

Cited by 288 publications

References 16 publications

Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non‐vascular smooth muscle: role of superoxide anions

Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non‐vascular smooth muscle: role of superoxide anions

Using guinea pigs in studies relevant to asthma and COPD

Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide‐like substance

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