The Role of Nitric Oxide in the Electrical Field Stimulation-Induced Contractions of Sphincter of Oddi and Gallbladder Strips in Guinea Pigs

Nitric oxide (NO) is a mediator of the vasodilation induced by a variety of physiological and pharmacological stimuli. The possible role of NO in the relaxation elicited in cerebral arteries by perivascular nerve stimulation has been investigated. Electrical field stimulation of precontracted bovine cerebral arteries induced a relaxation that was blocked by tetrodotoxin, but not by adrenergic or muscarinic receptor antagonists, suggesting the existence of nonadrenergic, noncholinergic dilator nerves, as has been shown in other species. The relaxation was significantly reduced by the inhibitors of NO synthesis, NG-monomethyl-L-arginine and nitro-L-arginine methyl ester, but not by the enantiomer, NG-monomethyl-D-arginine. Such a reduction was reversed by L-arginine. In addition, transmural nerve stimulation (TNS)-induced relaxation was potentiated by superoxide dismutase. No response to TNS was observed in arteries without endothelium. These results suggested that neurogenic relaxation of bovine cerebral arteries is mediated by endothelium-derived NO.

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Nitric oxide as putative nonadrenergic noncholinergic inhibitory transmitter in the opossum sphincter of Oddi

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y93-077 ◽

1993 ◽

Vol 71 (7) ◽

pp. 525-530 ◽

Cited By ~ 17

Author(s):

H. D. Allescher ◽

S. Lu ◽

E. E. Daniel ◽

M. Classen

Keyword(s):

Nitric Oxide ◽

Methylene Blue ◽

Sphincter Of Oddi ◽

Electrical Field Stimulation ◽

Inhibitory Effect ◽

Inhibitory Response ◽

Sphincter Muscle ◽

Field Stimulation ◽

Excitatory Effect ◽

Electrical Field

The sphincter of Oddi has a typical nonadrenergic noncholinergic inhibitory innervation; however, the transmitter of this inhibition has not been identified. The aim of the present study was to evaluate whether metabolites of the L-arginine – nitric oxide synthase pathway mediate neural inhibition in the sphincter of Oddi of the opossum. Electrical field stimulation at various frequencies (3, 5, and 10 pulses/s), performed in the presence of guanethidine (10−6 M) to exclude adrenergic responses, caused a slight, but significant excitatory response of the sphincter of Oddi. The responses were more pronounced at the duodenal side of the sphincter of Oddi than on the hepatic side. When the electrical field stimulation was repeated after blockading muscarinic receptors, using atropine (10−6 M), a potent inhibitory response was obtained. The inhibitory response to each of the various stimulation parameters was similar. Addition of L-arginine methyl ester (L-NAME, 2 × 10−4 M) abolished and reversed the inhibitory effect of electrical field stimulation, resulting in a potent stimulatory effect. Higher frequencies (5 and 10 pulses/s) were more potent in causing a stimulatory response than lower frequencies (3 pulses/s). The excitatory effect of electrical field stimulation was blocked or reversed to inhibition when the amino acid L-arginine (2 × 10−3 M) was added to the bath. In a second series of experiments, the inhibitory effect of electrical field stimulation in the presence of atropine and guanethidine was not prevented after the addition of methylene blue (5 × 10−5 M), a substance that, in vascular smooth muscle, has been demonstrated to block cyclic GMP dependent inhibitory responses. These data demonstrate that the sphincter of Oddi is characterized by an excitatory innervation that is partly cholinergic and partly nonadrenergic noncholinergic (NANC), while the NANC inhibitory response of this sphincter muscle is mediated by the release of endogenous nitric oxide or related compounds.Key words: nonadrenergic, noncholinergic, nitric oxide, L-arginine, sphincter of Oddi, methylene blue.

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Role Of Ca2+-Activated K+ Channel in the Neurogenic Contractions Induced by Electrical Field Stimulation in Detrusor Smooth Muscle Isolated from Rats and Guinea Pigs

Biophysical Journal ◽

10.1016/j.bpj.2009.12.682 ◽

2010 ◽

Vol 98 (3) ◽

pp. 125a-126a ◽

Cited By ~ 1

Author(s):

Whitney F. Kellett ◽

Georgi V. Petkov

Keyword(s):

Smooth Muscle ◽

Guinea Pigs ◽

Electrical Field Stimulation ◽

K Channel ◽

Field Stimulation ◽

Detrusor Smooth Muscle ◽

Electrical Field

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Pharmacologic responses of the mouse urinary bladder

Open Medicine ◽

10.2478/s11536-008-0082-2 ◽

2009 ◽

Vol 4 (2) ◽

pp. 192-197 ◽

Cited By ~ 1

Author(s):

A. Canda ◽

Christopher Chapple ◽

Russ Chess-Williams

Keyword(s):

Nitric Oxide ◽

Urinary Bladder ◽

Electrical Field Stimulation ◽

Inhibitory Effect ◽

Minor Role ◽

Detrusor Muscle ◽

Field Stimulation ◽

Muscarinic Agonists ◽

Electrical Field ◽

M3 Receptor

AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

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Nitric oxide as modulator of cholinergic neurotransmission in gastric muscle of rabbits

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.2.g456 ◽

1997 ◽

Vol 273 (2) ◽

pp. G456-G463 ◽

Cited By ~ 4

Author(s):

M. C. Baccari ◽

C. Iacoviello ◽

F. Calamai

Keyword(s):

Nitric Oxide ◽

Methyl Ester ◽

Substance P ◽

Electrical Field Stimulation ◽

Field Stimulation ◽

Electrical Field ◽

Prostaglandin F2 Alpha ◽

Fast Relaxation ◽

Gastric Muscle ◽

Relaxant Response

The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L-NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2 alpha), or carbachol (CCh), a fast relaxant response that, depending on stimulation frequency and strip tension, could be followed by a slower, sustained relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations and often reversed them into contractions; these effects were greatly counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to block the EFS-induced fast relaxations as the CCh concentration was increased. The NO synthesis inhibitors greatly reduced the sustained relaxant responses elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The results indicate that the NO synthesis inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway. The involvement of both VIP and NO in sustained relaxations is also suggested.

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Release of epithelium-derived PGE2 from canine trachea after antigen inhalation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.274.2.l220 ◽

1998 ◽

Vol 274 (2) ◽

pp. L220-L225 ◽

Cited By ~ 4

Author(s):

I. McGrogan ◽

L. J. Janssen ◽

J. Wattie ◽

P. M. O’Byrne ◽

E. E. Daniel

Keyword(s):

Smooth Muscle ◽

Electrical Field Stimulation ◽

Tracheal Smooth Muscle ◽

Organ Bath ◽

Field Stimulation ◽

Electrical Field ◽

Concentration Response Curve

To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10−9 to 10−5 M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2content. With the epithelium present, all three groups contracted similarly to 10−5 M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.

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Nitric oxide enhances contractile response of guinea-pig vas deferens to electrical field stimulation

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)48352-2 ◽

2000 ◽

Vol 82 ◽

pp. 222

Author(s):

Hironori Nakanishi ◽

Takako Chiba ◽

Tomoyuki Ono ◽

Isao Matsuoka

Keyword(s):

Nitric Oxide ◽

Guinea Pig ◽

Vas Deferens ◽

Contractile Response ◽

Electrical Field Stimulation ◽

Field Stimulation ◽

Electrical Field

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Role of cAMP and neuronal K+channels on α2-AR-induced inhibition of ACh release in equine trachea

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.274.5.l827 ◽

1998 ◽

Vol 274 (5) ◽

pp. L827-L832

Author(s):

Xiang-Yang Zhang ◽

Feng-Xia Zhu ◽

N. Edward Robinson

Keyword(s):

Electrical Field Stimulation ◽

Intracellular Camp ◽

Field Stimulation ◽

Ach Release ◽

Electrical Field ◽

K Channels ◽

Parasympathetic Nerves ◽

Pathway Activation ◽

Before And After

To investigate the effects of changes in intracellular cAMP on α2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the α2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca2+-activated K+ channels mediate α2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release. The amount of released ACh was measured by HPLC coupled with electrochemical detection. Clonidine (10−7 to 10−5 M) dose dependently inhibited ACh release before and after treatment with 8-bromo-cAMP (10−3 M) or forskolin (3 × 10−5M). ChTX and IBTX, both at the concentration of 5 × 10−7 M, significantly increased ACh release; however, they did not alter the magnitude of clonidine-induced inhibition. These results indicated that in equine tracheal parasympathetic nerves, α2-AR-induced inhibition of ACh release is via an intracellular cAMP-independent pathway. Activation of both ChTX- and IBTX-sensitive Ca2+-activated K+ channels inhibits the electrical field stimulation-evoked ACh release, but these channels are not involved in the α2-AR-induced inhibition of ACh release.

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