naloxone and Gastroesophageal-Reflux

Morphine increases residual lower esophageal sphincter (LES) pressure during swallow-induced LES relaxation to levels shown experimentally to prevent reflux. The hypothesis that morphine reduces reflux by increasing residual LES pressure during transient LES relaxation was tested in 8 healthy subjects and 8 patients with reflux disease.. Esophageal pH, LES, and esophageal pressures were recorded simultaneously during three sequential 30-minute periods, basal, after morphine, and after naloxone, while the stomach was distended by constant infusion of 10% dextrose.. Morphine decreased the number of reflux episodes and the time at pH < 4 in the patients (3.0 +/- 0.5 vs. 6.2 +/- 1.0 [P < 0.02] and 44% +/- 7% vs. 64% +/- 7% [P < 0.05], respectively) but not in the healthy subjects (P = NS). Transient LES relaxation was the major mechanism of reflux, and although morphine did not affect residual LES pressure during transient LES relaxations, it decreased their number markedly in the patients (3.0 +/- 0.5 vs. 6.6 +/- 1.7 [P < 0.05]) and marginally in the healthy subjects (2.1 +/- 0.4 vs. 2.6 +/- 0.4; P = NS). Naloxone completely reversed the effects of morphine.. Morphine reduces reflux in patients with reflux disease by decreasing the number of transient LES relaxations.

Topics: Adult; Aged; Analgesics, Opioid; Deglutition; Esophagogastric Junction; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Incidence; Injections, Intravenous; Male; Middle Aged; Morphine; Muscle Relaxation; Naloxone; Narcotic Antagonists; Pressure

1. Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Our previous results suggest that microvascular leakage induced, in the guinea-pig airways, by intra-oesophageal hydrochloric acid (HCl) infusion was mainly dependent on the release of tachykinins. Nociceptin, an endogenous ligand of the opioid receptor NOP, has been shown to inhibit bronchoconstriction and cough in guinea-pig or cat by inhibiting tachykinin release. 2. The purpose of this study was to investigate the effects of nociceptin on the intra-oesophageal HCl-induced airway microvascular leakage evaluated by Evans blue dye extravasation measurement in anaesthetised guinea-pigs pretreated with propranolol, atropine and phosphoramidon. 3. Infusion of intra-oesophageal HCl led to a significant increase in plasma extravasation in the main bronchi and trachea. This increase was abolished when animals underwent a bilateral vagotomy. 4. Airway microvascular leakage was inhibited by nociceptin (3-30 microg x kg(-1) i.v.) in a dose-dependent manner (maximal inhibition at the dose of 30 microg x kg(-1): 19.76+/-1.13 vs 90.92+/-14.00 ng x mg(-1) tissue for nociceptin and HCl infusion, respectively, in the main bronchi, P<0.01). The NOP receptor agonist [Arg(14),Lys(15)]N/OFQ mimicked the inhibitory effect of nociceptin, but at a 10-fold lower dose (3 microg x kg(-1) i.v). The NOP receptor antagonist J-113397 had no effect on plasma protein extravasation by itself, but was able to block the inhibitory effect of nociceptin. 5. Morphine (1 mg x kg(-1)) had a similar inhibitory effect as that of nociceptin. Naloxone pretreatment abolished the effect of morphine, but was enable to block the inhibitory effect of nociceptin. 6. Under similar conditions, nociceptin, in the previous range of concentration, was unable to counteract the airway microvascular leakage induced by substance P (SP). 7. These results suggest that airway plasma extravasation induced by intra-oesophageal HCl instillation might be inhibited by specific stimulation of the NOP receptor with nociceptin. Nociceptin is likely to act at a pre-junctional level, by inhibiting tachykinin release, since it was unable to prevent SP-induced airway plasma extravasation.

Topics: Animals; Benzimidazoles; Bronchi; Capillary Permeability; Disease Models, Animal; Gastroesophageal Reflux; Guinea Pigs; Hydrochloric Acid; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nociceptin; Opioid Peptides; Piperidines; Receptors, Opioid; Substance P; Trachea; Vagotomy; Vasodilator Agents

Topics: Benzamides; Chemical Phenomena; Chemistry; Cisapride; Dexamethasone; Digestive System; Domperidone; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Kinetics; Metoclopramide; Naloxone; Phenytoin; Piperidines; Proglumide; Vomiting