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Satish Rattan - One of the best experts on this subject based on the ideXlab platform.
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Role of alpha adrenoceptors in opossum Internal Anal Sphincter
2016Co-Authors: Shigeru Yamato, Satish RattanAbstract:The purpose of the present investigation was to examine the role of alpha adrenoceptors in the Internal Anal Sphincter (IAS). Studies were performed on alpha-chloralose anesthe-tized opossums. Resting pressure in the IAS (IASP) was re-corded using low compliant continuously perfused catheters. The effects of the alpha-i adrenoceptor agonist phenylephrine and alpha-2 adrenoceptor agonist clonidine and their corre-sponding selective antagonists, prazosin and yohimbine, re-spectively, were examined on the resting IASP, and on rectal balloon distension (RBD)-mediated IAS relaxation. Phenylephrine caused a rise in the IASP that was blocked by prazosin and not by yohimbine. Phenylephrine had no effect on IAS relaxation caused by RBD. Clonidine on the other hand caused significant suppression of IAS relaxation in response to RBD, but caused minimal changes in the resting IASP. The suppression of IAS relaxation by clonidine was selectively an-tagonized by yohimbine but not by prazosin. From these stud-ies we conclude that alpha-2 adrenoceptors exert important neuromodulatory influences on rectoAnal inhibitory reflex, while alpha-i adrenoceptors may exert modulatory effects on the resting IAS tone. (J. Clin. Invest. 1990. 86:424-429.) Key words: Internal Anal Sphincter- alpha adrenoceptors * recto-Anal inhibitory reflex * Anal cAnal pressure
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Bimodal effect of oxidative stress in Internal Anal Sphincter smooth muscle
American journal of physiology. Gastrointestinal and liver physiology, 2015Co-Authors: Jagmohan Singh, Sumit Kumar, Satish RattanAbstract:Changes in oxidative stress may affect basal tone and relaxation of the Internal Anal Sphincter (IAS) smooth muscle in aging. We examined this issue by investigating the effects of the oxidative st...
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Heme oxygenase-1 upregulation modulates tone and fibroelastic properties of Internal Anal Sphincter
American journal of physiology. Gastrointestinal and liver physiology, 2014Co-Authors: Chadalavada Vijay Krishna, Sumit Kumar, Jagmohan Singh, Satish RattanAbstract:A compromise in the Internal Anal Sphincter (IAS) tone and fibroelastic properties (FEP) plays an important role in rectoAnal incontinence. Herein, we examined the effects of heme oxygenase (HO)-1 ...
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cellular regulation of basal tone in Internal Anal Sphincter smooth muscle by rhoa rock
American Journal of Physiology-gastrointestinal and Liver Physiology, 2007Co-Authors: Chirag A. Patel, Satish RattanAbstract:Sustained contractions of smooth muscle cells (SMC) maintain basal tone in the Internal Anal Sphincter (IAS). To examine the molecular bases for the myogenic tone in the IAS, the present studies fo...
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Cellular regulation of basal tone in Internal Anal Sphincter smooth muscle by RhoA/ROCK.
American journal of physiology. Gastrointestinal and liver physiology, 2007Co-Authors: Chirag A. Patel, Satish RattanAbstract:Sustained contractions of smooth muscle cells (SMC) maintain basal tone in the Internal Anal Sphincter (IAS). To examine the molecular bases for the myogenic tone in the IAS, the present studies fo...
A Tøttrup - One of the best experts on this subject based on the ideXlab platform.
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Effects of transmural field stimulation in isolated smooth muscle of human rectum and Internal Anal Sphincter
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1997Co-Authors: E. B. Glavind, Axel Forman, G. Madsen, A TøttrupAbstract:Smooth muscle preparations from the circular muscle layer of the most distal rectum and the proximal and distal human Internal Anal Sphincter (IAS) mounted in organ baths to record isometric tensio...
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Pharmacological identification of different inhibitory mediators involved in the innervation of the Internal Anal Sphincter.
British journal of pharmacology, 1995Co-Authors: A Tøttrup, M. A. Knudsen, F. Hanberg Sorensen, E. B. GlavindAbstract:1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit Internal Anal Sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological Analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit Internal Anal Sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum Internal Anal Sphincter.
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Mechanical properties of isolated smooth muscle from human rectum and Internal Anal Sphincter
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1993Co-Authors: E. B. Glavind, D Svane, Axel Forman, G. Madsen, K-e Andersson, A TøttrupAbstract:The passive and active length-tension relations of the circular smooth muscle layer of the human distal rectum and the proximal and distal Internal Anal Sphincter were investigated. Muscle strips w...
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The role of nitrogen oxide synthesis for relaxation of the Internal Anal Sphincter
Ugeskrift for laeger, 1993Co-Authors: A Tøttrup, E. B. Glavind, D SvaneAbstract:The purpose of the present study was to examine the role of the L-arginine-nitric-oxide pathway in neurogenic relaxation of the Internal Anal Sphincter. Muscle strips representing the Internal Anal Sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometetric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxation induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) M), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous VIP was unaffected by N omega-nitro-L-arginine pretreatment, indicating that VIP relaxation does not utilize the L-argining-nitric oxide pathway. It is concluded that the non-adrenergic, non-cholinergic innervation of the Internal Anal Sphincter involves an inhibitory substance generated from the L-arginine--No pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.
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Involvement of the L-Arginine-Nitric Oxide Pathway in Internal Anal Sphincter Relaxation
Gastroenterology, 1992Co-Authors: A Tøttrup, E. B. Glavind, D SvaneAbstract:Abstract The purpose of this study was to examine the role of the l-arginine-nitric oxide pathway in neurogenic relaxation of the Internal Anal Sphincter. Muscle strips representing the Internal Anal Sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometric tension. N ω-nitro-l-arginine, an agent known to inhibit the l-arginine-nitric oxide pathway, concentration-dependently reduced relaxations induced by transmural field stimulation. At the highest concentration of N ω-nitro-l-arginine (10 −4 mol/L), no relaxation was evoked at any frequency tested (0.5–40 Hz). The inhibitory response to exogenous vasoactive intestinal polypeptide was unaffected by N ω-nitro-l-arginine pretreatment, indicating that vasoactive intestinal polypeptide relaxation does not use the l-arginine-nitric oxide pathway. In addition, responses to forskolin and sodium nitroprusside were not influenced by N ω-nitro-l-arginine preincubation, suggesting that the effect observed was not caused by a direct influence on the adenylate or the guanylate cyclases. It is concluded that the nonadrenergic, noncholinergic innervation of the Internal Anal Sphincter involves an inhibitory substance generated from the l-arginine-nitric oxide pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.
Ahmet Ayar - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effects of Sildenafil Citrate on the Tonus of Isolated Dog Internal Anal Sphincter
Diseases of the Colon & Rectum, 2005Co-Authors: Erhan Aygen, Cemalettin Camci, Ali Sait Durmus, Osman Dogru, Omer Topuz, Refik Ayten, Ahmet AyarAbstract:PURPOSE Although the exact pathogenesis of Anal fissure is not known, hypertonicity of the Internal Anal Sphincter might be involved in its pathogenesis as main event. To gain information about possible usefulness of the novel, smooth-muscle–relaxing drug, sildenafil, in chronic Anal fissure, we investigated the effect of sildenafil citrate on acetylcholine-induced contractility of Internal Anal Sphincter isolated from dogs. METHODS Internal Anal Sphincter strips were taken from German shepherd dogs and suspended in a tissue bath filled with Krebs solution at 37°C (pH 7.4) continuously bubbled with 95 percent oxygen and 5 percent carbon dioxide, and isometric contractions were recorded. Contractions were evoked by 10 μM acetylcholine, and the effects of different concentrations of sildenafil citrate (0.1, 0.3, and 1 mM) on the isometric tension of each Internal Anal Sphincter strip were examined. The statistical significance was Analyzed by one-way Analysis of variance. RESULTS Pretreatment with sildenafil citrate (0.1 mM) attenuated contractile response to acetylcholine (n = 3), which were significantly weak compared with the maximum contractile response to the acetylcholine alone (610 ± 110 mg vs . 2,825.17 ± 416 mg; n = 12; P < 0.05). Sildenafil citrate also significantly inhibited the acetylcholine-induced contractions in a dose-dependent manner when applied after. CONCLUSIONS This experimental in vitro study showed that sildenafil citrate relaxes acetylcholine stimulated contractions of isolated dog Internal Anal Sphincter. This may be of importance for raising the possibility that sildenafil cit-rate may have future potential in the treatment of chronic Anal fissure. Further studies are needed for a conclusive decision on possible usefulness of sildenafil citrate in patients with chronic Anal fissure.
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Inhibitory Effects of Sildenafil Citrate on the Tonus of Isolated Dog Internal Anal Sphincter
Diseases of the colon and rectum, 2005Co-Authors: Erhan Aygen, Cemalettin Camci, Ali Sait Durmus, Osman Dogru, Omer Topuz, Refik Ayten, Ahmet AyarAbstract:PURPOSE Although the exact pathogenesis of Anal fissure is not known, hypertonicity of the Internal Anal Sphincter might be involved in its pathogenesis as main event. To gain information about possible usefulness of the novel, smooth-muscle-relaxing drug, sildenafil, in chronic Anal fissure, we investigated the effect of sildenafil citrate on acetylcholine-induced contractility of Internal Anal Sphincter isolated from dogs. METHODS Internal Anal Sphincter strips were taken from German shepherd dogs and suspended in a tissue bath filled with Krebs solution at 37 degrees C (pH 7.4) continuously bubbled with 95 percent oxygen and 5 percent carbon dioxide, and isometric contractions were recorded. Contractions were evoked by 10 muM acetylcholine, and the effects of different concentrations of sildenafil citrate (0.1, 0.3, and 1 mM) on the isometric tension of each Internal Anal Sphincter strip were examined. The statistical significance was Analyzed by one-way Analysis of variance. RESULTS Pretreatment with sildenafil citrate (0.1 mM) attenuated contractile response to acetylcholine (n = 3), which were significantly weak compared with the maximum contractile response to the acetylcholine alone (610 +/- 110 mg vs. 2,825.17 +/- 416 mg; n = 12; P < 0.05). Sildenafil citrate also significantly inhibited the acetylcholine-induced contractions in a dose-dependent manner when applied after. CONCLUSIONS This experimental in vitro study showed that sildenafil citrate relaxes acetylcholine stimulated contractions of isolated dog Internal Anal Sphincter. This may be of importance for raising the possibility that sildenafil cit-rate may have future potential in the treatment of chronic Anal fissure. Further studies are needed for a conclusive decision on possible usefulness of sildenafil citrate in patients with chronic Anal fissure.
Michael A Kamm - One of the best experts on this subject based on the ideXlab platform.
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Injectable silicone biomaterial for faecal incontinence due to Internal Anal Sphincter dysfunction
Gut, 2002Co-Authors: N. J. Kenefick, Carolynne J. Vaizey, A. J. Malouf, Christine Norton, M. Marshall, Michael A KammAbstract:Background: A weak or disrupted Internal Anal Sphincter can cause passive faecal incontinence. Conservative measures may help some patients but there is no simple surgical solution for those who fail conservative treatment. A successful technique using trans-Sphincteric injection of a bulking agent to augment the Internal Anal Sphincter was developed in a previous pilot study. Aim: To determine the clinical results and underlying physiological effects of biomaterial injection. Patients: Six patients (four males, median age 53 years (range 36–65)) with faecal incontinence to solid or liquid stool related to poor Internal Anal Sphincter function, of varied aetiology, were recruited. Methods: Silicone based biomaterial injections were performed, under local anaesthesia, with antibiotic cover. Three injections were placed circumferentially, trans-Sphincterically, entering away from the Anal margin and injecting at or just above the dentate line. Anorectal physiological studies, endoAnal ultrasound, a bowel symptom diary, a validated incontinence score, and quality of life questionnaires were completed before treatment and on completion of follow up. Results: At a median follow up of 18 months (range 15–19), five of six patients had marked symptom improvement. Faecal incontinence scores improved from a median of 14/24 (range 11–20) before to 8/24 (6–15) after injection. Short form-36 quality of life physical and social function scores improved from a median of 26/100 (5–33) to 79/100 (25–100) and from 10/100 (5–37) to 100/100 (50–100), respectively. There was a corresponding physiological increase in maximum Anal resting and squeeze pressures. Ultrasound showed the Bioplastique to be retained in the correct position in the improved patients without migration. There were no complications. Conclusion: Trans-Sphincteric injection of silicone biomaterial can provide a marked improvement in faecal incontinence related to a weak or disrupted Internal Anal Sphincter. This is associated with improved Sphincter function and quality of life.
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Internal Anal Sphincter repair.
International journal of colorectal disease, 1997Co-Authors: Anne-marie Leroi, Michael A Kamm, J. Weber, Ph. Denis, P. R. HawleyAbstract:The results of repair to the Internal and Sphincter alone has been evaluated in five patients with persistent Anal incontinence following surgery which affected the Internal Anal Sphincter. All had passive incontinence for solid or liquid stool. Symptoms, anorectal manometry, and Anal endosonography were evaluated before and after surgery. After surgery three patients felt improved but had still persistent symptoms, and no patients achieved full continence. Three patients showed an increased maximal and resting pressure, but only one of them was within the normal range. Post operatively, all the Anal ultrasound scans showed a persistent Internal Sphincter defect, and two showed an unsuspected external Anal Sphincter defect. Although some patients felt symptomatically improved, the overall clinical, manometric and radiological findings after Internal and Sphincter repair were disappointing.
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Primary degeneration of the Internal Anal Sphincter as a cause of passive faecal incontinence.
Lancet (London England), 1997Co-Authors: Carolynne J. Vaizey, Michael A Kamm, Clive I BartramAbstract:Summary Background Faecal incontinence is usually attributed to pelvic-floor denervation of striated muscle or direct Sphincter trauma. We have identified a cause of passive faecal incontinence related to degeneration of the Internal Anal Sphincter smooth muscle, in the absence of denervation, structural damage, external-Sphincter weakness, or sensory abnormalities. Methods Patients were included on the basis of: passive faecal incontinence, no urge faecal incontinence, low Anal pressure whilst at rest, normal Anal-squeeze pressure, endosonographically confirmed circumferentially intact Internal and external Anal Sphincters, and normal pudendal nerve terminal nerve latencies. In a second Analysis done to assess the proportion of patients with this disorder, we recorded the cause of incontinence in consecutive patients seen during a 6-month period. Findings 45 patients (35 women, median age 63 years, range 23–80 years) fulfilled the diagnostic criteria. Median duration of symptoms was 2 years (3 months to 20 years). Nine of the 35 women were nulliparous. The median resting Anal pressure was 40 cm water (16–56 cm water, normal >60 cm water). Endosonography revealed an Internal Sphincter that was thin and hyperechogenic, and had a poorly defined edge. The normal increase in the thickness of the Internal Anal Sphincter with age was not seen. Anal-squeeze pressure, sensitivity, and pudendal nerve latencies were normal. In the second Analysis the condition was identified in eight of 230 patients, representing 4% of new referrals. Interpretation Primary degeneration of the Internal Anal Sphincter smooth muscle is a discrete clinical condition causing passive faecal incontinence.
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Abnormal Internal Anal Sphincter fibrosis and elasticity in fecal incontinence
Diseases of the colon and rectum, 1995Co-Authors: C. T. M. Speakman, Michael A Kamm, Charles H.v. Hoyle, Michael Swash, M. M. Henry, John Nicholls, Geoffrey BurnstockAbstract:PURPOSE: We aimed to investigate the changes in the proportion of collagen and in the elasticity of the Internal Anal Sphincter in patients with neurogenic fecal incontinence. METHODS: Collagen content was studied in ten patients with neurogenic fecal incontinence (mean age, 51.5 years) and ten controls (age, 58.6 years) using histologic techniques to determine differences between incontinence and health and to determine the effect of aging. Changes in elasticity were also measured in 8 controls (mean age, 63 years) and 13 patients with neurogenic incontinence (mean age, 60 years) by recording the in vitro length-tension relationship of the freshly excised Internal Anal Sphincter. RESULTS: Incontinent patients had a significantly higher collagen content than controls (55 percent vs.33 percent;P=0.013). In incontinent patients the amount of collagen and the patients' ages correlated significantly (P=0.001). There was a greater increase in stable tension per increase in muscle length in the strips from incontinent patients compared with controls. CONCLUSIONS: Changes in fibrous tissue content are likely to influence muscle tone and responsiveness of the Sphincter in fecal incontinence.
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prospective study of the extent of Internal Anal Sphincter division during lateral Sphincterotomy
Diseases of The Colon & Rectum, 1994Co-Authors: Abdul H Sultan, John R. Nicholls, Michael A Kamm, Clive I BartramAbstract:PURPOSE: The aim of lateral Internal Anal Sphincterotomy when treating Anal fissure is to divide the distal one-third to one-half of the Internal Anal Sphincter. This study aimed to evaluate prospectively the extent of disruption to the Internal Anal Sphincter following lateral Anal Internal Sphincterotomy and also to establish the prevalence of symptoms of Anal incontinence in these patients. METHODS: Fifteen patients with Anal fissure (ten females and five males) had bowel symptoms assessed and Anal endosonography performed preoperatively and two months after lateral Internal Anal Sphincterotomy. RESULTS: Anal endosonography was normal preoperatively in all but two females who had anterior external Sphincter defects (presumedly from previous obstetric trauma). Postoperatively, apart from one male in whom no defect could be identified, all had an Internal Anal Sphincter defect corresponding to the site of lateral Internal Anal Sphincterotomy. In nine of the ten females, the defect involved the full length of the Internal Anal Sphincter, but in the other four males, the defect involved the distal Internal Anal Sphincter only. All were continent preoperatively, but after lateral Internal Anal Sphincterotomy, three females became incontinent to flatus (two of whom had a preoperative external Sphincter defect). CONCLUSION: In contrast to lateral Internal Anal Sphincterotomy in males, division of the Internal Anal Sphincter in most females tends to be more extensive than intended. This is probably related to their shorter Anal cAnal. In some females, lateral Internal Anal Sphincterotomy may compromise Sphincter function and precipitate Anal incontinence, particularly in the presence of other Sphincter defects. Care should be exercised especially in the presence of previous obstetric trauma, as Internal Anal Sphincter division may further compromise Sphincter function.
E. B. Glavind - One of the best experts on this subject based on the ideXlab platform.
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Effects of transmural field stimulation in isolated smooth muscle of human rectum and Internal Anal Sphincter
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1997Co-Authors: E. B. Glavind, Axel Forman, G. Madsen, A TøttrupAbstract:Smooth muscle preparations from the circular muscle layer of the most distal rectum and the proximal and distal human Internal Anal Sphincter (IAS) mounted in organ baths to record isometric tensio...
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Pharmacological identification of different inhibitory mediators involved in the innervation of the Internal Anal Sphincter.
British journal of pharmacology, 1995Co-Authors: A Tøttrup, M. A. Knudsen, F. Hanberg Sorensen, E. B. GlavindAbstract:1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit Internal Anal Sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological Analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit Internal Anal Sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum Internal Anal Sphincter.
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Mechanical properties of isolated smooth muscle from human rectum and Internal Anal Sphincter
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1993Co-Authors: E. B. Glavind, D Svane, Axel Forman, G. Madsen, K-e Andersson, A TøttrupAbstract:The passive and active length-tension relations of the circular smooth muscle layer of the human distal rectum and the proximal and distal Internal Anal Sphincter were investigated. Muscle strips w...
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The role of nitrogen oxide synthesis for relaxation of the Internal Anal Sphincter
Ugeskrift for laeger, 1993Co-Authors: A Tøttrup, E. B. Glavind, D SvaneAbstract:The purpose of the present study was to examine the role of the L-arginine-nitric-oxide pathway in neurogenic relaxation of the Internal Anal Sphincter. Muscle strips representing the Internal Anal Sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometetric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxation induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) M), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous VIP was unaffected by N omega-nitro-L-arginine pretreatment, indicating that VIP relaxation does not utilize the L-argining-nitric oxide pathway. It is concluded that the non-adrenergic, non-cholinergic innervation of the Internal Anal Sphincter involves an inhibitory substance generated from the L-arginine--No pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.
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Involvement of the L-Arginine-Nitric Oxide Pathway in Internal Anal Sphincter Relaxation
Gastroenterology, 1992Co-Authors: A Tøttrup, E. B. Glavind, D SvaneAbstract:Abstract The purpose of this study was to examine the role of the l-arginine-nitric oxide pathway in neurogenic relaxation of the Internal Anal Sphincter. Muscle strips representing the Internal Anal Sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometric tension. N ω-nitro-l-arginine, an agent known to inhibit the l-arginine-nitric oxide pathway, concentration-dependently reduced relaxations induced by transmural field stimulation. At the highest concentration of N ω-nitro-l-arginine (10 −4 mol/L), no relaxation was evoked at any frequency tested (0.5–40 Hz). The inhibitory response to exogenous vasoactive intestinal polypeptide was unaffected by N ω-nitro-l-arginine pretreatment, indicating that vasoactive intestinal polypeptide relaxation does not use the l-arginine-nitric oxide pathway. In addition, responses to forskolin and sodium nitroprusside were not influenced by N ω-nitro-l-arginine preincubation, suggesting that the effect observed was not caused by a direct influence on the adenylate or the guanylate cyclases. It is concluded that the nonadrenergic, noncholinergic innervation of the Internal Anal Sphincter involves an inhibitory substance generated from the l-arginine-nitric oxide pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.