The obligatory role of host microbiota in bioactivation of dietary nitrate

Moretti, Chiara; Zhuge, Zhengbing; Zhang, Gensheng; Haworth, Sarah McCann; Paulo, Luciano Leite; Guimarães, Drielle D.; Cruz, José Jaime da; Montenegro, Marcelo F.; Cordero-Herrera, Isabel; Braga, Valdir A.; Weitzberg, Eddie; Carlström, Mattias; Lundberg, Jon O.

doi:10.1016/j.freeradbiomed.2019.10.003

Cited by 26 publications

(14 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These studies seem to confirm much earlier studies on ex vivo mammalian liver/muscle homogenates suggesting that XOR may exhibit nitrate-reducing capability (Bernheim and Dixon, 1928;Ward et al, 1985Ward et al, , 1986. In contrast, very recently, Moretti et al (2019) have published findings suggesting a lack of mammalian nitrate reductase activity in germ-free mice in a separate study, indicating some heterogeneity in studies with animals rendered "germ-free." Irrespective, the presence and importance of putative nitrate reductases in human physiology is yet to be firmly established.…”

Section: Prokaryotic Nitratesupporting

confidence: 84%

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

et al. 2020

View full text Add to dashboard Cite

Section: Prokaryotic Nitratesupporting

confidence: 84%

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

et al. 2020

View full text Add to dashboard Cite

“…(a) In prepubertal rats, HH increased nitric oxide (NO) production by vascular endothelial cells through their own endothelial NOS (eNOS), triggering, by negative feedback over the nucleus of the surrounding myocytes, a reduction of mRNA and nitric oxide synthase (NOS) synthesis (dashed boxes). That reduction in NO production by NOS might be compensated by xanthine oxidoreductase (XOR), which would produce NO from the nitrite-nitrate (Nx) reservoir, coming largely from the diet (Moretti et al, 2019) and possibly also from the previously oxidized vascular NO mentioned above. This maintains normal intracellular NO levels, resulting in a maintenance of mitochondrial and contractile function [left ventricular develop pressure (LVDP)] as in normoxic conditions, preventing the development of endogenous cardioprotection (LVDP dashed box).…”

Section: Mechanical and Energetic Responses In The Whole Heartmentioning

confidence: 99%

Acute hypobaric hypoxia and cardiac energetic response in prepubertal rats: Role of nitric oxide

Padula

Czerniczyniec

Bonazzola

et al. 2021

Experimental Physiology

View full text Add to dashboard Cite

Studies in our laboratory showed that exposure of rats to hypobaric hypoxia (HH) increased the tolerance of the heart to hypoxia-reoxygenation (H/R), involving mitochondrial and cytosolic nitric oxide synthase (NOS) systems. The objective of the present study was to evaluate how the degree of somatic maturation could alter this healthy response. Prepubertal male rats were exposed for 48 h to a simulated altitude of 4400 m in a hypobaric chamber. The mechanical energetic activity in perfused hearts and the contractile functional capacity of NOS in isolated left ventricular papillary muscles were evaluated during H/R. Cytosolic nitric oxide (NO), production of nitrites/nitrates (Nx), expression of NOS isoforms, mitochondrial O 2 consumption and ATP production were also evaluated. The left ventricular pressure during H/R was not improved by HH. However, the energetic activity was increased. Thus, the contractile economy (left ventricular pressure/energetic activity) decreased in HH. Nitric oxide did not modify papillary muscle contractility after H/R. Cytosolic p-eNOS-Ser1177 and inducible NOS expression were decreased by HH, but no changes were observed in NO production. Interestingly, HH increased Nx levels, but O 2 consumption and ATP production in mitochondria were not affected by HH. Prepubertal rats exposed to HH preserved cardiac contractile function, but with a high energetic cost, modifying contractile economy. Although this could be related to the decreased NOS expression detected, cytosolic NO production was preserved, maybe through the Nx metabolic pathway, without modification of mitochondrial ATP production and O 2 consumption.

show abstract

“…First, although serum nitrate/nitrite levels were increased in the nitrate supplemented mouse groups, bioactive levels of NO were not directly measured [24,66,67]. Second, the conversion of nitrate to NO by the entero-salivary pathway is influenced by the bacterial composition of both the oral cavity and gut but this was not evaluated in the present study [14,[68][69][70]. In this regard, it is possible that there are species-and/ or strain-specific differences between the microbiome of humans and mice held in an artificial laboratory environment that alter the efficiency of NO generation from dietary nitrate [71,72].…”

Section: Plos Onementioning

confidence: 75%

“…However, previous in vivo studies in Han:SPRD PKD rats demonstrated that L-arginine only had marginal benefits on reducing kidney weight and cyst volume in males with no effect on BP [13]. This modest effect may be because of the low dose used (0.5 g/L) [13], and/or reduced bioavailability due to first pass metabolism [14]. To further clarify efficacy, in this study, we compared the effects of L-arginine and SNP in vitro, and found that they both reduced cyst diameter whereas L-NAME exacerbated it, and interestingly, by similar magnitudes.…”

Section: Plos Onementioning

confidence: 95%

“…In non-genetic ortholog rat models of PKD, the endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) proteins were downregulated in cyst-lining epithelial cells [10,11]. In the Han:SPRD Cy rat model, L-arginine (a substrate for NOS via the well-established L-arginine-NOS pathway [12]) increased NO metabolites, but the therapeutic efficacy on cystic kidney disease was mild [13], possibly due to first-pass metabolism [14]. In contrast, treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, a pan-NOS inhibitor) had more consistent findings and resulted in exacerbation of cystic kidney disease and hypertension [13,15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease

et al. 2021

View full text Add to dashboard Cite

Augmentation of endogenous nitric oxide (NO) synthesis, either by the classical L-arginine-NO synthase pathway, or the recently discovered entero-salivary nitrate-nitrite-NO system, may slow the progression of autosomal dominant polycystic kidney disease (ADPKD). To test this hypothesis, the expression of NO in human ADPKD cell lines (WT 9–7, WT 9–12), and the effect of L-arginine on anin vitromodel of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygousPkd1RC/RCmice (a hypomorphic genetic ortholog of ADPKD) received either low, moderate or high dose sodium nitrate (0.1, 1 or 10 mmol/kg/day), or sodium chloride (vehicle; 10 mmol/kg/day), supplemented drinking water from postnatal month 1 to 9 (n = 12 per group).In vitro, intracellular NO, as assessed by DAF-2/DA fluorescence, was reduced by >70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuatedin vitrocyst growth by up to 18%. In contrast, inPkd1RC/RCmice, sodium nitrate supplementation increased serum nitrate/nitrite levels by ~25-fold in the high dose group (P<0.001), but kidney enlargement and percentage cyst area was not altered, regardless of dose. In conclusion, L-arginine has mild direct efficacy on reducing renal cyst growthin vitro, whereas long-term sodium nitrate supplementation was ineffectivein vivo. These data suggest that the bioconversion of dietary nitrate to NO by the entero-salivary pathway may not be sufficient to influence the progression of renal cyst growth in ADPKD.

show abstract

The obligatory role of host microbiota in bioactivation of dietary nitrate

Cited by 26 publications

References 45 publications

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

Acute hypobaric hypoxia and cardiac energetic response in prepubertal rats: Role of nitric oxide

Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease

Contact Info

Product

Resources

About