Lower Esophageal Sphincter Is Achalasic in nNOS−/− and Hypotensive in W/Wv Mutant Mice

Sivarao, Digavalli V.; Mashimo, Hiroshi; Thatte, Hemant S.; Goyal, Raj K.

doi:10.1053/gast.2001.25541

Cited by 151 publications

(184 citation statements)

References 31 publications

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“…9,39,40 Also, knockout mice lacking nNOS exhibit a hypertonic LES with impaired relaxation on swallowing similar to that observed in achalasia patients. 36 These observations could explain our results showing association between eNOS, iNOS, and nNOS gene polymorphisms and achalasia. Our study showed that eNOS4a4a genotype of 27-bp VNTR polymorphism was associated with achalasia as compared with the presence of eNOS4b4b genotype.…”

Section: Discussionsupporting

confidence: 61%

“…4,33,34 Achalasia is known to result from degeneration of these inhibitory neurones, which are mostly nitrinergics. [35][36][37] In this study, we examined whether degeneration of inhibitory neurones, mostly nitrinergic, may be associated with polymorhism in NOS gene. NOS gene have several polymorphisms such as 27-bp VNTR polymorphism of eNOS, a biallelic polymorphism in exon 16 of iNOS gene and in exon 29 of nNOS.…”

Section: Discussionmentioning

confidence: 99%

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Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

Singh

Ghoshal

Misra

et al. 2015

J Neurogastroenterol Motil

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Background/AimsAchalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), produced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic polymorphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS). MethodsConsecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. Results Among ConclusionsAchalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

Singh

Ghoshal

Misra

et al. 2015

J Neurogastroenterol Motil

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“…Effect of L-NAME on vagal stimulated pyloric activity was studied within 20 minutes after its injection. 22 …”

Section: Drugsmentioning

confidence: 99%

Pyloric Sphincter Dysfunction in nNOS−/− and W/Wv Mutant Mice: Animal Models of Gastroparesis and Duodenogastric Reflux

2008

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“…Hence the lack of reduction in tone was not due to the inability of neurotransmitters to reach the smooth muscle cells but rather due to lack of active tone. Interestingly, in the W/W v mice in vivo, a low LES resting tone was observed (15). In contrast to responses in control tissue, N G -nitro-L-arginine (L-NNA) not only reduced the inhibitory effect of nerve stimulation but revealed a strong noncholinergic excitatory innervation, revealed by marked contraction of the musculature in response to nerve stimulation (Fig.…”

mentioning

confidence: 95%

“…Burns et al (1) and Ward et al (20) provided evidence that ICC-IM are the principal pathway from inhibitory nerves to smooth muscle cells, making the argument that neurotransmitters, in particular nitric oxide, released from nerve endings would not reach smooth muscle cells, because the distance would be sufficient to cause neurotransmitter inactivation. However, in vivo studies came to the conclusion that an inhibitory reflex mediated by nitric oxide, namely relaxation of the lower esophageal sphincter (LES) on swallowing, was still present in mutant mice (W/W v ) that have an abnormal c-kit gene and lack ICC-IM in the LES (15).…”

mentioning

confidence: 99%

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

Huizinga

Liu²,

Fitzpatrick³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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The motility of the gastrointestinal tract is generated by smooth muscle cells and is controlled to a large extent by an intrinsic neural network. A gap of ∼200 nm usually separates nerve varicosities from smooth muscle cells, which suggests that direct innervation of the smooth muscle by synapses does not occur. Enteric nerves do make synapse-like contact with proposed regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in gap junction contact with smooth muscle cells. The role played by ICC in enteric innervation is controversial. Experimental evidence has been presented in vitro for the hypothesis that nitrergic inhibitory innervation is strongly reduced in the absence of ICC. However, in vivo data appear to dispute that. The present report provides evidence that explains the discrepancy between in vivo and in vitro data and provides evidence that inhibitory neurotransmitters can reach smooth muscle cells without hindrance when ICC are absent. The fundic musculature shows increased responses to substance P-mediated innervation and shows marked spontaneous activity, which is consistent with increased muscle excitability.

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Lower Esophageal Sphincter Is Achalasic in nNOS−/− and Hypotensive in W/Wv Mutant Mice

Cited by 151 publications

References 31 publications

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

Pyloric Sphincter Dysfunction in nNOS−/− and W/Wv Mutant Mice: Animal Models of Gastroparesis and Duodenogastric Reflux

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

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