Introduction: Recent studies showed that sodium nitrite decreases blood pressure (BP) in two kidney, one clip (2K1C) hypertension, probably as a result of nitrite being converted into nitric oxide in the acid environment of the stomach. This study aimed at examining whether increasing gastric pH with omeprazol reduces the chronic antihypertensive effects of nitrite. Methods: 2K1C hypertensive and sham operated control rats were treated with omeprazole (10mg/Kg; i.p.) or vehicle and sodium nitrite (15mg/Kg; gavage) or saline for two weeks. Systolic BP (SBP) was measured by tail pletismografy weekly. Circulating nitrite levels were measured by chemiluminesce and gastric pH was measured with an electrode. The results were analyzed by two-way ANOVA. The results are show as mean ± standard deviation. Results: 2K1C rats were hypertensive two weeks after surgery (SBP=180±17 mmHg). After 4 weeks of treatment, nitrite exerted antihypertensive effects in rats treated with vehicle (SBP=161±23 mmHg versus 200±29 mmHg, respectively, in the 2K1C+nitrite and in the 2K1C+saline groups; P<0.05). However, nitrite exerted no antihypertensive effects in 2K1C rats treated with omeprazole (SBP=200±34 mmHg; P>0.05 versus 2K1C+saline group). We found no significant differences among the sham operated groups. Similar increases in plasma nitrite concentrations were found when animals treated with nitrite and omeprazol were compared with those treated with nitrite and vehicle (8.5±4.1 versus 5.2±3.6 μM, respectively; P>0.05). Omeprazole increased gastric pH in all animals treated with this drug (P<0.05). Conclusion Treatment with omeprazole blunts the chronic antihypertensive effects of sodium nitrite in 2K1C rats. However, this effect is probably not associated with significant differences in plasma nitrite concentrations.