Sodium nitrite, a potent relaxant of rat stomach fundus: in vitro evidence.
The effects of sodium nitrite (0.1, 1, 10 mM) on mechanical activity of isolated rat stomach fundus muscle and the influence of guanylate cyclase activity inhibitor (methylene blue) and channel inhibitors (tetrodotoxin, charybdotoxin, apamin) were studied. Nitrite evoked dose-dependent relaxation in the longitudinal and circular muscle layers. The lowest effective concentration of sodium nitrite was 0.1 mM, which is comparable with the NOAEL (no observed adverse effect level). Tetrodotoxin (1 microM) markedly inhibited electrically induced contraction and rebound relaxation, but did not influence the nitrite-induced relaxation. Charybdotoxin (100 nM) decreased the relaxation evoked by 10 mM nitrite to 52.3 and 65.7% of control reaction in the circular and longitudinal muscle layer, respectively. Apamin (100 nM) did not influence the nitrite-induced relaxation. Methylene blue (10 microM) decreased relaxation induced by nitrite in the longitudinal and circular muscle layer, respectively, to 66.7 and 54.3% of the response to 1 mM nitrite alone. Relaxation induced by nitrite was decreased in the presence of L-cysteine (5 mM), and in the circular and longitudinal muscle layer reached 29.6 and 23.1%, respectively, of the response to 1 mM nitrite alone. We conclude that the relaxing effect of nitrite on gastric fundus results from its direct action on smooth muscle cells and probably the enteric nervous system is not involved in this action. The nitrite-elicited relaxation depends on activation of guanylate cyclase and high conductance Ca2+-activated potassium channels; however, activation of potassium channels might be a part of or might act in parallel with the mechanism involving the cyclic GMP system. Effects of nitrite observed in the presence of L-cysteine suggest that nitrosothiols are not responsible for nitrite-evoked activation of guanylate cyclase.
Ceregrzyn
M
M
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland. ceregrzyn@alpha.sggw.waw.pl
Ozaki
T
T
Kuwahara
A
A
Wiechetek
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D009153:Mutagens; D014665:Vasodilator Agents; D018999:Charybdotoxin; D001030:Apamin; D013779:Tetrodotoxin; D003545:Cysteine; D012977:Sodium Nitrite; D000109:Acetylcholine; D008751:Methylene Blue