Inorganic nitrate and the cardiovascular system

Kapil, Vikas; Webb, David J.; Ahluwalia, Amrita

doi:10.1136/hrt.2009.180372

Cited by 80 publications

(79 citation statements)

References 97 publications

(92 reference statements)

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“…It has been suggested that the cardio-protective effects of diets rich in fruit and vegetables might be linked to their high inorganic nitrate (NO 3 -) content [7][8][9]. Vegetable consumption accounts for 60-80% of dietary NO 3 -intake [10] with leafy-green vegetables (e.g., spinach and lettuce varieties) and beetroot being particularly rich in NO 3 - [7].…”

Section: Introductionmentioning

confidence: 99%

Improvement in blood pressure after short-term inorganic nitrate supplementation is attenuated in cigarette smokers compared to non-smoking controls

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Improvement in blood pressure after short-term inorganic nitrate supplementation is attenuated in cigarette smokers compared to non-smoking controls

et al. 2016

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“…However, there are structurally dissimilar NO donors with different chemical reactivities and metabolic characteristics. More recently, novel signaling molecules, including nitrite (NO 2 Ϫ ) anions; alternative NO delivery strategies, such as NO gas for inhalation; or hybrid NOS gene and progenitor cell transfer approaches showed promising results in preclinical testing and are gradually introduced in clinical trials (61,86,100,148).…”

Section: No Donorsmentioning

confidence: 99%

Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

Zhang¹,

Janssens

Wingler

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang Y, Janssens SP, Wingler K, Schmidt HH, Moens AL. Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy. Am J Physiol Heart Circ Physiol 301: H634 -H646, 2011. First published May 27, 2011 doi:10.1152/ajpheart.01315.2010.-The pathogenesis of many cardiovascular diseases is associated with reduced nitric oxide (NO) bioavailability and/or increased endothelial NO synthase (eNOS)-dependent superoxide formation. These findings support that restoring and conserving adequate NO signaling in the heart and blood vessels is a promising therapeutic intervention. In particular, modulating eNOS, e.g., through increasing the bioavailability of its substrate and cofactors, enhancing its transcription, and interfering with other modulators of eNOS pathway, such as netrin-1, has a high potential for effective treatments of cardiovascular diseases. This review provides an overview of the possibilities for modulating eNOS and how this may be translated to the clinic in addition to describing the genetic models used to study eNOS modulation.endothelial nitric oxide synthase uncoupling; modulators; superoxide; tetrahydrobiopterin; enhancers; nitric oxide donors THE REVALENCE AND SEVERITY of incipient or overt cardiovascular diseases associated with reduced nitric oxide (NO) bioavailability has resulted in efforts to restore and conserve adequate NO signaling in the heart and blood vessels through therapeutic interventions. In the cardiovascular system, the signaling molecule NO, which is produced by the enzyme endothelial NO synthase (eNOS, NOS3), has a crucial role in maintaining normal vascular function, mediated by its vasodilating capacity and through a variety of antiatherogenic effects. eNOS is not only expressed in endothelial cells of the heart and blood vessels, in both atrial and ventricular myocytes, but also in specialized pacemaker tissue.Uncoupling of bioactive, i.e., dimeric eNOS to an inactive monomeric form (73) is caused by oxidative stress, which reduces the bioavailability of tetrahydrobiopterin (BH 4 ), an essential cofactor of eNOS. In this uncoupled state, NADPH consumption and oxygen reduction are uncoupled from L-arginine oxidation and NO formation with a subsequently decreased NO production and increased superoxide generation (157). eNOS generated superoxide, further oxidizes BH 4 , and hence enhances the uncoupling of eNOS. However, it is unclear which source of superoxide initiates eNOS uncoupling.Uncoupling of eNOS has been described in 1) situations associated with endothelial dysfunction such as atherosclerosis (3, 70), diabetes mellitus (135), ischemia-reperfusion (I/R) injury (35,138), hypertension (68), and chronic flow overload (78); 2) cardiac hypertrophy with ventricular remodeling (133); and 3) diastolic heart failure (149). eNOS also uncouples physiologically. For example, eNOS may uncouple postnatal in the lung, possibly leading to a developmental adaptation of the pulmonary vascular system to produce reactive oxygen species (ROS) (81). In addition, it ...

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“…Inorganic nitrate is present in most vegetables and is especially abundant in green leafy vegetables and beetroot (Beta vulgaris). Small-scale clinical studies demonstrate that orally-ingested inorganic nitrate is sequentially bioactivated, within the enterosalivary circuit, to inorganic nitrite (NO 2 − ) 7 which is then, in turn, converted to the signaling molecule nitric oxide (NO) within the systemic circulation. Although the reduction of nitrate to nitrite is not a response of the host, but rather a reaction facilitated by facultative bacteria that have colonized the dorsal surface of the tongue, 8 the reduction of nitrite to NO is a host response.…”

mentioning

confidence: 99%

Enhanced Vasodilator Activity of Nitrite in Hypertension

et al. 2013

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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.

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Inorganic nitrate and the cardiovascular system

Cited by 80 publications

References 97 publications

Improvement in blood pressure after short-term inorganic nitrate supplementation is attenuated in cigarette smokers compared to non-smoking controls

Improvement in blood pressure after short-term inorganic nitrate supplementation is attenuated in cigarette smokers compared to non-smoking controls

Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

Enhanced Vasodilator Activity of Nitrite in Hypertension

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