Effect of nitrite on blood pressure in anaesthetized and free-moving rats

Vleeming, W.; Kuil, A. van de; Biesebeek, J.D. te; Meulenbelt, Jan; Boink, A. B. T. J.

doi:10.1016/s0278-6915(97)00015-x

Cited by 42 publications

(26 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, Classen et al (8) reported that a nitrate-derived NO formation pathway is a possible mechanism for the hypotensive effect of vegetable-and fruit-rich diets. It was also reported that intravenous infusion of sodium nitrite decreased the blood pressure of anesthetized rats in a dose-dependent manner (38). These observations have stimulated our interest in nitrite as a dietary factor with potential for lowering blood pressure and preventing organ damage.…”

Section: Discussionmentioning

confidence: 87%

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Kanematsu

Yamaguchi²,

Ohnishi³

et al. 2008

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in N -nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME ϩ nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (ironnitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 Ϯ 8.9 vs. L-NAME 6.0 Ϯ 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAMEinduced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.vegetables; N -nitro-L-arginine methyl ester; kidney NITRIC OXIDE (NO) is a gaseous signaling molecule and exerts a variety of biological actions under physiological and pathophysiological conditions, such as regulation of the cardiovascular, inflammation, immune, and neuronal systems. NO also has numerous important functions in the kidney, such as the regulation of renal hemodynamics and glomerular microcirculation, the regulation of salt balance, the blunting of tubuloglomerular feedback, and the modulation of renal sympathetic nerve activity (18,26). Chronic blockade of nitric oxide synthases (NOSs) with N -nitro-L-arginine methyl ester (L-NAME) in rats results in severe hypertension and progressive kidney damage (3, 11). On the other hand, NO production seems to be low in chronic kidney disease (CKD) patients, and NO deficiency may play a role in CKD progression (5, 32). Treatment strategies to maintain the circulating NO level in healthy young people may be useful in preventing or slowing the progression of renal diseases.It is believed that NO is synthesized from L-arginine, NADPH, tetrahydrobiopterin, and the molecular oxygen catalyzed by NOSs in endothelial and other cells. The biological activity of NO is terminated by oxidation into nitrite and nitrate. Therefore, nitrite and nitrate in the blood are recognized as waste forms of NO. However, this dogma is now being challe...

show abstract

Section: Discussionmentioning

confidence: 87%

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Kanematsu

Yamaguchi²,

Ohnishi³

et al. 2008

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…[18][19][20] Studies have shown that the NO-like effects of nitrate are blocked if bacterial nitrate reduction in the mouth is abrogated with an antiseptic mouthwash, indicating that nitrite is an obligate intermediate in nitrate bioactivation. 21,22 Direct administration of nitrite to humans or animals has demonstrated many similar effects as nitrate, including protection against ischemia-reperfusion injury and [23][24][25] vasodilatory, 26,27 antihypertensive, [28][29][30][31][32] and metabolic effects. 33,34 Several pathways have been described for the reduction of nitrite to more bioactive nitrogen Abstract-Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides that affect blood pressure.…”

mentioning

confidence: 99%

Blood Pressure–Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor

et al. 2017

View full text Add to dashboard Cite

A n association between chronic use of proton pump inhibitors (PPIs) and increased risk of cardiovascular disease has been implicated. [1][2][3][4][5] For example, it seems that PPIs reduce the efficacy of antiplatelet drugs such as clopidogrel by competing with the hepatic isoenzyme CYP2C19, thereby interfering with its capacity to inhibit platelet aggregation. 6 Other studies have associated chronic use of PPI with increased cardiovascular risk, independently of treatment with clopidogrel 4 or CYP2C19 metabolism. 7,8 In addition, a recent study in diabetic patients indicates that PPIs increase blood pressure. 9 The mechanisms behind these effects are still unclear, but a reduced vascular bioavailability of NO has been suggested. 1 Moreover, it has been speculated that bioactivation of some antiplatelet drugs requires gastric nitrosation under acidic conditions. 10,11 We and others have been studying an alternative NO synthase-independent pathway for NO generation in which inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides in blood and tissues to affect cardiovascular function, including blood pressure.12 Dietary nitrate is absorbed rapidly and is extracted from blood by the salivary glands and greatly concentrated in saliva. In the mouth, commensal bacteria reduce nitrate to the more reactive nitrite anion. Nitrite is then swallowed and enters the acidic stomach where it is nonenzymatically metabolized further to form several potentially bioactive nitrogen oxides, including NO. Orally ingested nitrate clearly has robust NO-like effects systemically, including a decrease in blood pressure, [13][14][15] Abstract-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 −1 min −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 vascula...

show abstract

“…10,11 Accordingly, systemic nitrite administration causes dosedependent decreases in BP in both healthy animals and volunteers. [12][13][14][15] In addition, chronic oral administration of nitrite reduces BP without any evidence of tachyphylaxis in genetic, surgical, and salt-induced animal models of hypertension, [16][17][18][19][20] although in general the doses of nitrite tested substantially exceed physiological levels. However, the vascular nitrite reductase that underpins these BP-lowering effects has not been established.…”

mentioning

confidence: 99%

Enhanced Vasodilator Activity of Nitrite in Hypertension

et al. 2013

View full text Add to dashboard Cite

Abstract-Elevation of circulating nitrite (NO 2 − ) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects and the underpinning mechanisms persist in hypertension is unknown. Therefore, we investigated the consequences of systemic nitrite elevation in spontaneously hypertensive rats and conducted proofof-principle studies in patients. Nitrite caused dose-dependent blood pressure-lowering that was profoundly enhanced in spontaneously hypertensive rats versus normotensive Wistar Kyoto controls. This effect was virtually abolished by the xanthine oxidoreductase (XOR) inhibitor, allopurinol, and associated with hypertension-specific XOR-dependent nitrite reductase activity localized to the erythrocyte but not the blood vessel wall. To determine whether these pathways translate to human hypertension, we investigated the effects of elevation of circulating nitrite levels in 15 drug naïve grade 1 hypertensives. To elevate nitrite, we used a dose of dietary nitrate (≈3.5 mmol) that elevated nitrite levels ≈1.5-fold (P<0.01); a rise shown previously to exert no significant blood pressure-lowering effects in normotensives. This dose caused substantial reductions in systolic (≈12 mm Hg) and diastolic blood pressures (P<0.001) and pulse wave velocity (P<0.05); effects associated with elevations in erythrocytic XOR expression and XOR-dependent nitrite reductase activity.

show abstract

Effect of nitrite on blood pressure in anaesthetized and free-moving rats

Cited by 42 publications

References 4 publications

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Blood Pressure–Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor

Enhanced Vasodilator Activity of Nitrite in Hypertension

Contact Info

Product

Resources

About