Esophageal smooth muscle reactivity is impaired in chronic reflux esophagitis by both receptor- and nonreceptor-mediated mechanisms.

AIM: Esophagitis is associated with an impaired esophageal peristalsis. A few studies have been aimed at understanding the pathophysiology of abnormal peristaltic activity. The mechanism of impaired esophageal smooth muscle reactivity in the chronic gastroesophageal reflux (GER) model is investigated in vitro for the first time. MATERIALS AND METHODS: The chronic GER rat model was created by partial gastric outlet obstruction. The histopathological findings related to esophagitis were evaluated. Smooth muscle strips of the tunica muscularis mucosa of esophagus were studied in standard organ chambers. Carbachol- and KCl-induced contractile responses and serotonin- and papaverine- induced relaxant responses in both reflux and sham-operated control groups were determined. RESULTS: Histopathologically, chronic reflux esophagitis was observed in all specimens of the reflux group. Contractile (carbachol- and KCl-induced) smooth muscle responses were significantly decreased in the reflux group. When compared to control group, relaxant response of smooth muscle to serotonin was also significantly decreased in the reflux group. However, there was no difference in papaverine-induced relaxant responses between 2 groups. CONCLUSIONS: Our study describes the effects of chronic GER on rat esophageal smooth muscle contractility in vitro. We found that both receptor- (carbachol, serotonin) and nonreceptor-mediated (KCl) esophageal smooth muscle reactivity were impaired in chronic reflux esophagitis. These changes may correspond to the functional motor abnormalities of the esophagus seen in patients with chronic reflux esophagitis.

Effect of chronic renal failure on foregut smooth muscle reactivity: an experimental study.

PURPOSE: An association between chronic renal failure (CRF) and gastroesophageal reflux (GER) is well known. The aim of this study was to pharmacologically characterize and investigate the possible contribution of smooth muscle reactivity pathways involving GER on the CRF rat model. MATERIAL AND METHODS: Chronic renal failure was created in Sprague-Dawley rats by 5 of 6 nephrectomy. The rats were divided into 2 groups: the CRF-induced group (CRF group) and the sham-operated group (control group). Esophageal smooth muscle strips were studied in vitro for their contractile (KCl, carbachol) and relaxant (isoproterenol, serotonin, and papaverine) response to receptor activation in the organ chambers set up. Subsequently, the in vitro lower esophageal sphincter (LES) smooth muscle study was generated by KCl, carbachol, isoproterenol, nicotine, sodium nitroprusside (SNP), and papaverine. RESULTS: Compared with controls, esophageal strips taken from CRF-induced rats associated with decreased smooth muscle responses to carbachol, serotonin, and increased response to KCl. Isoproterenol- and papaverine-induced relaxant responses were not affected. Contractility of the isolated LES strips were significantly increased to KCl and carbachol in the CRF group compared with the control group. Similar relaxant responses were obtained in LES strips stimulated by isoproterenol, SNP, and papaverine in the CRF and control group. Nicotine-induced relaxant responses were decreased in the CRF group compared with the control group. CONCLUSIONS: Our study revealed alterations of receptor-dependent esophageal and LES smooth muscle reactivity in the CRF-induced rats. Impaired foregut smooth muscle reactivity may contribute to the development of GER-related functional abnormalities in patients with CRF.

Impaired gastric motility in the gastroesophageal reflux rat model: an in vitro study.

PURPOSE: The present study investigated the effects of acid and mixed reflux on the responsiveness of gastric smooth muscle in the gastroesophageal reflux (GER) rat model. MATERIAL AND METHODS: Three groups of rat were studied encompassing acid reflux, mixed reflux and sham operation. Acid reflux was induced by pyloric ligation (AR group) and mixed reflux was induced by jejunal ligation 1 cm distal to Treitz ligament (MR group). Similar surgical manipulations were carried out in the sham operated rats (SO group). Carbachol-, serotonin-, KCl-induced contractile response and nicotine-, sodium nitroprusside-, papaverine-induced relaxant response in isolated gastric fundus smooth muscle strips were determined using in vitro muscle technique 24 h after surgery. RESULTS: Isolated gastric fundus smooth muscle contractility to serotonin, carbachol or KCl was significantly reduced in the AR and MR groups with decreased Emax and pD(2) values compared with the SO group. Relaxant responses to nicotine was significantly increased in the AR and MR groups with increased Emax and pD(2) values compared with the SO group. Sodium nitroprusside and papaverine-induced-relaxant responses were similar in all of the groups and there was no change in agonist potency. CONCLUSION: The present study indicates that decreased contractile and increased nicotine-induced relaxant response of the gastric smooth muscle in the surgically created GER model. These findings suggest that impaired gastric smooth muscle reactivity at least in part may play a role in gastric dysmotility in GER.

Development changes esophageal smooth muscle reactivity: an in vitro study.

This study was designed to determine if age related changes occur in esophageal smooth muscle reactivity in developing rats. Esophageal smooth muscle strips were obtained from three groups of rats: neonatal (1-3 days old), 1-month-old (30-35 days old) and young adults (4 months old). Esophageal smooth muscle reactivity was assessed in vitro by organ chamber experiments. Concentration-response curves were analyzed for differences in smooth muscle reactivity. Contractile response to cholinergic agonist carbachol increased in the neonatal group with increased maximum contraction compared to the other groups. However, there was no change in pD(2) value among the groups. Maximum contraction evoked by KCl was also significantly increased in the neonatal group compared to the adult group. Relaxation responses elicited by beta adrenoceptor agonist isoproterenol and 5-hydroxytryptamine (5-HT) receptor agonist serotonin were increased in the neonatal group with increased E(max) and pD(2) values compared to the other groups. The present study indicates that the neonatal esophageal smooth muscle responds to serotonergic, adrenergic and cholinergic agonists to a significantly greater degree than the adult esophageal smooth muscle.

Esophagitis impairs esophageal smooth muscle reactivity in the rat model: an in vitro study.

The present study investigated how reflux-induced esophagitis affects the smooth muscle reactivity of the esophageal body. Two different esophagitis models were used: acid gastric and mixed duodenogastric reflux. All test animals apart from the controls developed gross and histologic evidence of esophagitis. Contractile (carbachol and KCI) and relaxant (isoproterenol) esophageal smooth muscle responses were significantly decreased in the presence of acid- and mixed reflux-induced esophagitis. Similar relaxant responses to serotonin and papaverine were found in the three groups. Our study demonstrated impaired esophageal smooth muscle reactivity when esophagitis was induced by acid or mixed reflux. These changes may correspond to the functional motor abnormalities of the esophagus seen in patients with reflux esophagitis.