Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats.

BACKGROUND: Dietary nitrates are known to produce nitric oxide in the stomach, which may influence gastric function. AIM: To investigate whether nitrate ingestion modifies gastric sensitivity to distension through a mechanism involving nitric oxide production. METHODS: Nociception, associated with gastric distension ranging from 10 to 40 mmHg, was assessed in anaesthetized rats by the amplitude of cardiovascular depressor responses. Gastric volume corresponding to each distension was recorded. The following intragastric administrations (1 mL) were performed before distension: water (control), KNO3, NaNO3, KCl, NaCl (all at 0.1 mmol/kg), standard food (0.5 g), sodium nitroprusside, a nitric oxide donor (5 mg/kg), and haemoglobin, a nitric oxide scavenger (150 mg/kg) given either with water or KNO3. RESULTS: In controls, the fall in blood pressure increased from 7.8 +/- 2.0 to 31.6 +/- 2. 7 mmHg at distending pressures from 10 to 40 mmHg, respectively. KNO3 significantly reduced the amplitude of blood pressure response for the highest distending pressures (35 and 40 mmHg), while KCl induced a reduction in blood pressure response at all gastric pressures. NaNO3 and NaCl did not induce significant changes in distension-induced depressor responses. Administration of 0.5 g of standard food or sodium nitroprusside reproduced the effect of KNO3, which was reversed by haemoglobin. None of the compounds modified the gastric pressure-volume relationship, except KNO3, which increased gastric volume for the lowest distending pressures, and haemoglobin, which reduced the volume for the highest pressure. CONCLUSIONS: Ingestion of potassium nitrate reduces the sensitivity to gastric distension, through a mechanism involving nitric oxide.

Decrease in gastric sensitivity to distension by 5-HT1A receptor agonists in rats.

Using an in vivo model for evaluation of gastric sensitivity in awake rats, we aimed to determine whether 5-hydroxytryptamine 1A (5-HT1A) agonists modify pain threshold and gastric compliance specifically through 5-HT1A receptors. Isobaric gastric distensions were performed with a barostat using steps of 5 mm Hg in male rats equipped with a gastric balloon and electrodes implanted in the neck muscles. Gastric distension at 15 or 20 mm Hg induced a typical posture associated with contractions of the neck muscles. Rats received drugs 30 min before gastric distension. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), administered intraperitoneally (0.5 mg/kg) increased gastric pain threshold and gastric tone. These effects were reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricular administration of the 5-HT1A antagonist WAY 100635. Flesinoxan (4 mg/kg, intraperitoneally), another 5-HT1A agonist reproduced the effects of 8-OH-DPAT on pain threshold and gastric tone and the alpha2-receptor antagonist yohimbine did not modify the action of 8-OH-DPAT. Our results indicate that activation of 5-HT1A receptors at the level of the central nervous system increases gastric tone and decreases gastric sensitivity to distension.

A model for evaluation of gastric sensitivity in awake rats.

We developed a model for the evaluation of gastric sensitivity to distension in awake rats. A balloon made from a latex condom was chronically placed in the stomach and three stainless steel electrodes were implanted in the neck muscles. Isobaric distensions were performed with a barostat by step of 5 mmHg with 10 min inflation and 2 min deflation. Gastric pressure, integrated neck electromyogram (EMG) and gastric volume were continuously monitored on a potentiometric recorder. Gastric distension at 15 or 20 mmHg induced a typical posture associated with contractions of the neck muscles. Pain threshold was defined as the pressure inducing an increase of integrated neck EMG greater than 100%. The mean pain threshold was 18.5 +/- 0.7 mmHg and was not modified 2, 4 and 7 days after the first experiment. However, gastric volumes were significantly higher on the 4th and the 7th days. Morphine at the doses of 0.4 and 4 mg kg-1 i.p. significantly increases the pain threshold. At the doses of 0.04 and 0.4 mg kg-1, morphine significantly increased gastric volume for the distending pressure of 10 mmHg. Naloxone (2.5 mg kg-1 i.p.) reversed the effects of morphine. In conclusion, our model permits simultaneous evaluation of pain threshold and gastric compliance associated with gastric distension in conscious rats.

[Role of 5-HT3 receptors in the control by cholecystokinin of transient relaxations of the inferior esophageal sphincter in dogs]. / Rôle des récepteurs 5-HT3 dans le contrôle par la cholécystokinine des relaxations transitoires du sphincter inférieur de l'oesophage chez le chien.

AIMS: The aim of this study was to determine, using specific antagonists, whether 5-HT3 receptors participate in triggering transient lower esophageal sphincter relaxations, independently or in relation with their CCKergic control. METHODS: Esophageal, lower esophageal sphincter and fundus pressure were manometrically monitored in 5 conscious dogs. Gastric distensions with air at constant pressure (1.0 and 1.7 kPa) were performed during 30 min under IV infusion of CCK8S (0.5 microgram/kg/h) or NaCl 9/1000 and were preceded (10 min) by IV administration of 5-HT3 receptors antagonists (ondansetron 0.2-500 micrograms/kg and granisetron 100 micrograms/kg) or NaCl 9/1000. RESULTS: The number of transient relaxations induced by a 1.7 kPa gastric distension (7.9 +/- 0.4/30 min) was dose-dependently reduced by ondansetron (1-100 micrograms/kg) and by granisetron (100 micrograms/kg). Ondansetron (100 micrograms/kg) did not modify the number of relaxations under a 1.0 kPa gastric pressure (2.7 +/- 0.4 vs 2.6 +/- 0.4/30 min) but reduced the increase of the occurrence of relaxations induced by CCK8S under a gastric pressure of 1.0 and 1.7 kPa. CONCLUSION: These results suggest that the CCK control in triggering transient lower esophageal sphincter relaxations is modulated by serotonin via 5-HT3 receptors subtypes.