Nitric oxide, prostaglandin, and sensory neurons in gastric mucosal blood flow response during acid secretion in rats.
1. The mechanism underlying the increase of gastric mucosal blood flow (GMBF) during acid secretion induced by pentagastrin was investigated in anesthetized rats, in relation to nitric oxide (NO), prostaglandin (PG), and sensory neurons. 2. An intravenous infusion of pentagastrin at 60 micrograms/kg/h (submaximal dose) produced an increase of acid secretion and GMBF as determined by laser Doppler flowmetry, and the GMBF response was totally attenuated when the acid secretion was inhibited by omeprazole or when the luminal H+ was removed by mucosal perfusion with glycine (200 mM). 3. Prior administration of NG-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, IV), a NO synthase inhibitor, significantly mitigated the GMBF response to pentagastrin, without any influence on acid secretion, and this effect was antagonized by coadministration of L-arginine (500 mg/kg IP). 4. The increase of GMBF during pentagastrin infusion also was significantly mitigated by indomethyacin (5 mg/kg, SC) or sensory deafferentation following capsaicin pretreatment, had no effect on the acid secretion, and was totally inhibited by the combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. 5. Pentagastrin infusion for 8 hr did not by itself cause any macroscopic damage in the stomach, but additional treatments with L-NAME, and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. 6. These results suggest that the increase of GMBF induced by submaximal dose of pentagastrin totally depends on luminal H+. This process seems to be mediated by endogenous NO and PGs, as well as capsaicin-sensitive sensory neurons, and to play a pivotal role in maintaining mucosal integrity during acid secretion.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Hirata
T
T
Takeuchi
K
K
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009853:Omeprazole / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology*; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D054328:Proton Pump Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010418:Pentagastrin; D009853:Omeprazole; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin