{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:27:08Z","timestamp":1788582428980,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>\n            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\u00d740 mg) before ingesting sodium nitrite (0.3 mg kg\n            <jats:sup>\u22121<\/jats:sup>\n            ), followed by blood pressure monitoring. Nitrite reduced systolic blood pressure by a maximum of 6\u00b11.3 mm\u2009Hg 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\n            <jats:sup>\u22121<\/jats:sup>\n            min\n            <jats:sup>\u22121<\/jats:sup>\n            ) intravenously. Interestingly, although plasma nitrite peaked at similar levels as with orally ingested nitrite (\u22481.8 \u00b5mol\/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\u2013lowering 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\u2013nitrite\u2013NO pathway.\n          <\/jats:p>","DOI":"10.1161\/hypertensionaha.116.08081","type":"journal-article","created":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T02:13:21Z","timestamp":1477966401000},"page":"23-31","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Blood Pressure\u2013Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor"],"prefix":"10.1161","volume":"69","author":[{"given":"Marcelo F.","family":"Montenegro","sequence":"first","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela L.","family":"Sundqvist","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip J.","family":"Larsen","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbing","family":"Zhuge","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Carlstr\u00f6m","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Weitzberg","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon O.","family":"Lundberg","sequence":"additional","affiliation":[{"name":"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 \u00c5strand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (F.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003602"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.261"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61525-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-153-6-201009210-00005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007964"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124653"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.032912"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d2690"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2714-y"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.08.045"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.09.022"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2466"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.153536"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.103523"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc062800"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.115.116244"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.06.031"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.079491"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.004"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2007.01713.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.01.011"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2008.08.003"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402927101"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00036.2004"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22493"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm954"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.009554"},{"key":"e_1_3_4_29_2","first-page":"258","article-title":"Antihypertensive effect of oral nitrite uptake in the spontaneously hypertensive rat.","volume":"45","author":"Beier S","year":"1995","unstructured":"Beier S, Classen HG, Loeffler K, Schumacher E, Th\u00f6ni H. 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