nitroarginine and Constipation

Colonic electrical stimulation (CES) may have a therapeutic potential for slow transit constipation (STC). This study aimed to evaluate the effects of implantable CES on gastrointestinal transit and defecation, and explore its mechanisms in a canine STC model.. Two pairs of electrodes were implanted in each of the proximal colon and rectosigmoid junction (RSJ). Parameters were individualized according to the symptoms of the stimulated dogs. In the STC model, gastrointestinal transit and defecation were assessed to evaluate the effects of double-site CES, and of double-site CES combined with atropine or N-nitro-L-arginine (L-NNA) in a crossover design.. Individualized parameters varied among the animals. The CES significantly shortened gastrointestinal transit time (GITT) and colonic transit time (CTT) compared with sham CES (p = 0.001 and p < 0.001, respectively). Compared with sham CES, the CES also exhibited significantly higher stool frequency and stool consistency score (p = 0.018 and p = 0.001, respectively). Co-treatment with atropine or L-NNA blocked the effects of CES on GITT, CTT, and stool consistency. The stool frequency increased by CES, however, only reduced by co-treatment with L-NNA.. This double-site implantable CES can improve the gastrointestinal transit and defecation in a canine STC model, possibly by activating the cholinergic and nitrergic pathways. The CES mode used in this study may be proven feasible in treating STC.

Topics: Analysis of Variance; Animals; Atropine; Cholinergic Agents; Colon; Constipation; Defecation; Disease Models, Animal; Dogs; Electric Stimulation; Electrodes, Implanted; Enzyme Inhibitors; Female; Gastrointestinal Diseases; Gastrointestinal Transit; Muscarinic Antagonists; Nitroarginine; Radiography

Emodin is traditionally used as a laxative and is found to increase or decrease the contractility of intestinal smooth muscle in low doses and high doses, respectively. In this study, we propose that bidirectional regulation (BR) on the contractility of jejunal smooth muscle (CJSM) is inducible by emodin in the absence of control by the central nervous system. The results indicated that emodin-induced BR had the following characteristics. A stimulatory effect on CJSM was induced by emodin at 7 low contractile states, and an inhibitory effect was induced on CJSM at 7 high contractile states. Emodin-induced BR on myosin phosphorylation was also observed. BR was not observed in the presence of tetrodotoxin, suggesting that enteric nervous system is required for producing BR. The stimulatory effect of emodin on CJSM was abolished by atropine and diphenhydramine, respectively, suggesting that BR was correlated with cholinergic and histamine system while jejunal smooth muscle was at low contractile state. The inhibitory effect of emodin on CJSM was abolished by phentolamine, propranolol, and L-NG-nitroarginine (L-NNA), respectively, suggesting that BR was related to adrenergic hyperactivity and with a nitric oxide relaxing mechanism while jejunal smooth muscle was in a high contractile state. The exact mechanism, however, needs further investigation.

Topics: Animals; Atropine; Constipation; Diarrhea; Diphenhydramine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Emodin; Enteric Nervous System; In Vitro Techniques; Jejunum; Laxatives; Muscle Contraction; Muscle, Smooth; Myosins; Nitroarginine; Phentolamine; Phosphorylation; Propranolol; Rats; Rats, Sprague-Dawley; Tetrodotoxin

The cause of dysmotility in patients with slow-transit constipation is unknown. Nitric oxide has recently been shown to be a neurotransmitter in the nonadrenergic, noncholinergic inhibitory nerves of the human gut. To clarify the physiologic significance of nitric oxide in the colon of patients with slow-transit constipation, we investigated the enteric nerve responses in lesional and normal bowel segments derived from patients with slow-transit constipation and patients who underwent colon resection for colonic cancers.. Twenty-six preparations were taken from colonic lesions in eight patients with slow-transit constipation (2 men; age, 23 to 69 (mean, 44.8) years). Forty-two preparations were taken from the normal colons of 14 patients with colonic cancer (8 men; age, 40 to 66 (mean, 52.4) years). A mechanographic technique was used to evaluate in vitro muscle responses to electric field stimulation before and after treatment with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine.. The colons of patients with slow-transit constipation were more strongly innervated by nonadrenergic, noncholinergic inhibitory nerves than were normal colons (P <0.05). Nitric oxide was found to act on both normal and slow-transit constipation colons. The colons of patients with slow-transit constipation were more strongly innervated by nitric oxide nerves than were normal colons (P < 0.01). Responses to electric field stimulation were the same in each case among the normal colons and were also the same in each case among the slow-transit constipation colons.. These findings suggest that an increase of nitric oxide mediates nonadrenergic, noncholinergic inhibitory nerves and plays an important role in the dysmotility observed in the colons of patients with slow-transit constipation.

Topics: Adult; Aged; Arginine; Colon; Constipation; Electric Stimulation; Enteric Nervous System; Female; Humans; Male; Middle Aged; Muscle, Smooth; Neurotransmitter Agents; Nitric Oxide; Nitroarginine