Blood Pressure-Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor.
Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides that affect blood pressure. The mechanisms for nitrite bioactivation are unclear, but recent studies in rodents suggest that gastric acidity may influence the systemic effects of this anion. In a randomized, double-blind, placebo-controlled crossover study, we tested the effects of a proton pump inhibitor on the acute cardiovascular effects of nitrite. Fifteen healthy nonsmoking, normotensive subjects, aged 19 to 39 years, were pretreated with placebo or esomeprazole (3×40 mg) before ingesting sodium nitrite (0.3 mg kg-1), followed by blood pressure monitoring. Nitrite reduced systolic blood pressure by a maximum of 6±1.3 mm Hg when taken after placebo, whereas pretreatment with esomeprazole blunted this effect. Peak plasma nitrite, nitrate, and nitroso species levels after nitrite ingestion were similar in both interventions. In 8 healthy volunteers, we then infused increasing doses of sodium nitrite (1, 10, and 30 nmol kg-1min-1) intravenously. Interestingly, although plasma nitrite peaked at similar levels as with orally ingested nitrite (≈1.8 µmol/L), no changes in blood pressure were observed. In rodents, esomeprazole did not affect the blood pressure response to the NO donor, DEA NONOate, or vascular relaxation to nitroprusside and acetylcholine, demonstrating an intact downstream NO-signaling pathway. We conclude that the acute blood pressure-lowering effect of nitrite requires an acidic gastric environment. Future studies will reveal if the cardiovascular complications associated with the use of proton pump inhibitors are linked to interference with the nitrate-nitrite-NO pathway.
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Marcelo F
MF
Montenegro
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Michaela L
ML
Sundqvist
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Filip J
FJ
Larsen
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Zhengbing
Z
Zhuge
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Mattias
M
Carlström
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.).
Eddie
E
Weitzberg
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (M.F.M., M.S., Z.Z., M.C., E.W., J.O.L.); and Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.). jon.lundberg@ki.se.
Jon O
JO
Lundberg
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
D009566:Nitrates; D054328:Proton Pump Inhibitors; C031618:sodium nitrate; D064098:Esomeprazole
blood pressure; esomeprazole; nitrate; nitric oxide; nitrite; proton pump inhibitors