Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats.
The new pathway nitrate-nitrite-nitric oxide (NO) has emerged as a physiological alternative to the classical enzymatic pathway for NO formation from l-arginine. Nitrate is converted to nitrite by commensal bacteria in the oral cavity and the nitrite formed is then swallowed and reduced to NO under the acidic conditions of the stomach. In this study, we tested the hypothesis that increases in gastric pH caused by omeprazole could decrease the hypotensive effect of oral sodium nitrite. We assessed the effects of omeprazole treatment on the acute hypotensive effects produced by sodium nitrite in normotensive and L-NAME-hypertensive free-moving rats. In addition, we assessed the changes in gastric pH and plasma levels of nitrite, NO(x) (nitrate+nitrite), and S-nitrosothiols caused by treatments. We found that the increases in gastric pH induced by omeprazole significantly reduced the hypotensive effects of sodium nitrite in both normotensive and L-NAME-hypertensive rats. This effect of omeprazole was associated with no significant differences in plasma nitrite, NO(x), or S-nitrosothiol levels. Our results suggest that part of the hypotensive effects of oral sodium nitrite may be due to its conversion to NO in the acidified environment of the stomach. The increase in gastric pH induced by treatment with omeprazole blunts part of the beneficial cardiovascular effects of dietary nitrate and nitrite.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970 Campinas, SP, Brazil.
Lucas C
LC
Pinheiro
Marcelo F
MF
Montenegro
Jefferson H
JH
Amaral
Graziele C
GC
Ferreira
Alisson M
AM
Oliveira
Jose E
JE
Tanus-Santos
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005750:Gastric Juice / Q000737:chemistry* / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000097:blood; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols / Q000097:blood; D012977:Sodium Nitrite / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects
D000897:Anti-Ulcer Agents; D000959:Antihypertensive Agents; D001565:Benzoates; D016166:Free Radical Scavengers; D007093:Imidazoles; D026403:S-Nitrosothiols; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D009853:Omeprazole; D012977:Sodium Nitrite; D019331:NG-Nitroarginine Methyl Ester