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Am J Physiol Gastrointest Liver Physiol 283: G1360-G1367, 2002; doi:10.1152/ajpgi.00168.2002
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Vol. 283, Issue 6, G1360-G1367, December 2002

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

Sara Calatayud2, Eugenia García-Zaragozá1, Carlos Hernández1, Elsa Quintana1, Vicente Felipo3, Juan Vicente Esplugues1, and María Dolores Barrachina1

1 Departmento de Farmacología, Universidad de Valencia; 2 Unidad Mixta de Investigación, Hospital Clínico/Universidad de Valencia; and 3 Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, 46010 Valencia, Spain

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 NG-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 N6-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.

nitric oxide; prostaglandins; antrum pylorus; nutrient meals


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