<scp>l</scp>-Arginine-induced relaxation of the internal anal sphincter is not mediated by nitric oxide

Acheson, AG; Griffin, Nicholas R.; Scholefield, J H; Wilson, V.G.

doi:10.1002/bjs.4182

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…The use of L-arginine as a treatment for anal fissures was first studied in 2002 [15] when it was shown to significantly reduce anal tone. In 2003, the effect of L-arginine on myogenic tone was found to be independent of nitric oxide [16]. An alternative mode of action has not been suggested, however.…”

Section: L-argininementioning

confidence: 77%

“…Larginine, a precursor of nitric oxide, has been found to relax IAS smooth muscle perhaps by increasing substrate for nitric oxide synthase (NOS). Topical L-arginine has been shown to significantly reduce anal tone in one study [15], although puzzlingly Acheson et al have shown that the effect of Larginine on myogenic tone is independent of nitric oxide [16].…”

Section: Physiology and Pathophysiology Of The Internal Anal Sphinctermentioning

confidence: 98%

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A review of chronic anal fissure management

Collins

Lund

2007

Tech Coloproctol

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Anal fissure management has rapidly progressed in the last 15 years as our understanding of fissure pathophysiology has developed. All methods of treatment aim to reduce the anal sphincter spasm associated with chronic anal fissures. Surgical techniques have been used for over 100 years with success. Lateral internal sphincterotomy remains the surgical treatment of choice for many practitioners. Postoperative impairment of continence remains controversial. Recently, less invasive methods of treatment have been explored. Topical nitrates, calcium channel blockers and botulinum toxin are established treatments. These and other non-surgical treatments are described in this review. Various guidelines and treatment algorithms for anal fissure are also discussed.

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Section: L-argininementioning

confidence: 77%

Section: Physiology and Pathophysiology Of The Internal Anal Sphinctermentioning

confidence: 98%

A review of chronic anal fissure management

Collins

Lund

2007

Tech Coloproctol

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“…Acheson et al [11] recently reported the ability of Larginine to reduce myogenic tone, independently of nitric oxide. Not only L-arginine but also D-arginine and other basic amino acids caused a concentration-dependent reduction in myogenic tone of the internal anal sphincter.…”

Section: Discussionmentioning

confidence: 99%

“…This effect was partially dependant of the pH of the solution but the osmolality of the solution was the predominant factor in anal sphincter relaxation. Acheson et al [11] concluded that hyperosmolar solutions given rectally can be used to treat anal hypertonia.…”

Section: Discussionmentioning

confidence: 99%

The effect of oral administration of L–arginine on anal resting pressure and anodermal blood flow in healthy volunteers

et al. 2005

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“…Based on an in vitro study, Acheson and coauthors concluded that the ability of L-arginine to reduce myogenic tone is independent of NO. 33 According to these authors, the L-arginine-induced relaxation is osmolality-dependent. The difference between in vitro and in vivo observations raises the possibility that L-arginine may increase NO formation in a cell type not present in vitro, such as vascular endothelial cells of the larger blood vessels in the perianal region, which are removed during dissection.…”

Section: Discussionmentioning

confidence: 98%

Treatment of Chronic Anal Fissure by Application of l-Arginine Gel: A Phase II Study in 15 Patients

Gosselink

Darby

Zimmerman

et al. 2005

Diseases of the Colon &Amp; Rectum

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PURPOSE: Local application of exogenous nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes fissure healing by reducing anal resting pressure and improving anodermal blood flow. The major drawback of these nitric oxide donors is headache. The overall incidence of this side effect is approximately 40 percent. Recently we have shown in healthy volunteers that L-arginine, being an intrinsic precursor of nitric oxide, reduces anal resting pressure without headache as a side effect. The aim of the present study was to evaluate the effect of L-arginine on anal resting pressure, anodermal blood flow, and fissure healing in patients with chronic anal fissure. METHODS: Fifteen patients with a chronic anal fissure were included in the present study. Before entering the study 10 patients were unsuccessfully treated by local application of isosorbide dinitrate. Six of these patients experienced severe headache during treatment with isosorbide dinitrate. All patients were treated for at least 12 weeks by local application of a gel containing L-arginine 400 mg/ml five times a day. In patients with a persistent fissure, treatment was continued until 18 weeks. Anal manometry and laser Doppler flowmetry of the anoderm were performed before treatment, 20 minutes after local application of the first dose, and after 12 weeks of treatment. A visual analog scale was used to assess fissurerelated pain and headache. RESULTS: One patient dropped out after one day of treatment, and one was excluded because of violation of the study protocol. After 12 weeks of treatment complete fissure healing was observed in 3 of 13 (23 percent) patients, and after 18 weeks the healing rate was 8 of 13 (62 percent) patients. None of the 13 patients experienced typical nitric oxide-induced headache. The pressure recordings showed a significant reduction of maximum anal resting pressure (mean ± SD): pretreatment 89 ± 17 mmHg; 20 minutes after application of the first dose 67 ± 17 mmHg; 12 weeks after treatment 74 ± 14 mmHg (P < 0.005). Recordings of anodermal blood flow showed a significant increase in flow: pretreatment 0.36 ± 0.25 volts; 20 minutes after application of the first dose 0.59 ± 0.27; 12 weeks after treatment 0.64 ± 0.33 (P < 0.005). CONCLU-SIONS: Local application of L-arginine promotes fissure healing without headache as a side effect, and L-arginine is effective even in patients not responding to isosorbide dinitrate treatment. [

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l-Arginine-induced relaxation of the internal anal sphincter is not mediated by nitric oxide

Abstract: The ability of L-arginine to reduce myogenic tone is independent of nitric oxide. This effect may be partially pH dependent but the osmolality of the solution appears to be a major factor. Hyperosmolar solutions might be worthy of further investigation as agents that affect anal tone.

Cited by 8 publications

References 20 publications

A review of chronic anal fissure management

A review of chronic anal fissure management

The effect of oral administration of L–arginine on anal resting pressure and anodermal blood flow in healthy volunteers

Treatment of Chronic Anal Fissure by Application of l-Arginine Gel: A Phase II Study in 15 Patients

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