6533b871fe1ef96bd12d1a97

RESEARCH PRODUCT

Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying

Eugenia García-zaragozáCarlos HernándezJuan V. EspluguesMaria D. BarrachinaSara CalatayudVicente FelinoElsa Quintana

subject

MalePhysiologymedicine.medical_treatmentIndomethacinNitric Oxide Synthase Type IINitric Oxide Synthase Type IprostaglandinsRats Sprague-Dawleychemistry.chemical_compoundPyloric AntrumEnzyme InhibitorsAntrumSulfonamidesArachidonic AcidbiologyReverse Transcriptase Polymerase Chain ReactionStomachdigestive oral and skin physiologyGastroenterologyNitric oxide synthasemedicine.anatomical_structureNG-Nitroarginine Methyl EsterQuinacrinenutrient mealsantrum. pylorusmedicine.medical_specialtyIndazolesIntraperitoneal injectionNitric OxidePhospholipases ANitric oxidenitric oxidePhysiology (medical)Internal medicinemedicineAnimalsCyclooxygenase InhibitorsRNA MessengerNitrobenzenesHepatologyGastric emptyingPylorusdigestive system diseasesRatsEndotoxinsEndocrinologyPyloric AntrumchemistryGastric EmptyingFoodbiology.proteinProstaglandinsNitric Oxide Synthase

description

A single intraperitoneal injection of endotoxin (40 μg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N G-nitro-l-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N 6-iminoethyl-l-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantly prevented delay in gastric emptying induced by endotoxin but failed to modify gastric emptying in vehicle-treated animals. Ca2+-dependent NOS activity in the antrum pylorus of the stomach was diminished by endotoxin, whereas Ca2+-independent NOS activity was not changed. In addition, decreased nNOS mRNA and protein were observed in the antrum pylorus of endotoxin-treated rats. Our results suggest that downregulation of nNOS in the antrum pylorus of the stomach and synthesis of prostaglandins mediate the delay in gastric emptying of a solid nutrient meal induced by endotoxin.

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