Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats

• Published in: Free radical biology & medicine 2012-08, Vol.53 (4), p.701-709
• Main Authors: Pinheiro, Lucas C., Montenegro, Marcelo F., Amaral, Jefferson H., Ferreira, Graziele C., Oliveira, Alisson M., Tanus-Santos, Jose E.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Ulcer Agents - pharmacology; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - antagonists & inhibitors; antihypertensive effect; Aorta - drug effects; Aorta - physiopathology; bacteria; Benzoates - pharmacology; Blood Pressure - drug effects; Free Radical Scavengers - pharmacology; Free radicals; Gastric Juice - chemistry; Gastric Juice - drug effects; Hydrogen-Ion Concentration; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Imidazoles - pharmacology; In Vitro Techniques; L-NAME; Male; mouth; NG-Nitroarginine Methyl Ester; nitrates; nitric oxide; Nitric Oxide - blood; Nitrite; Omeprazole; Omeprazole - pharmacology; Rats; Rats, Wistar; S-Nitrosothiols - blood; sodium nitrite; Sodium Nitrite - administration & dosage; Sodium Nitrite - antagonists & inhibitors; stomach; Vasodilation - drug effects
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2012.06.001

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, NOx (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, NOx, 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. [Display omitted] ► The nitrate–nitrite–NO pathway is a physiological source of NO. ► Nitrite exerts antihypertensive effects. ► Nitrite is reduced to NO under the acidic conditions of the stomach. ► Omeprazole increases gastric pH and reduces the hypotensive effects of nitrite. ► Omeprazole may blunt beneficial cardiovascular effects of dietary nitrite.