scholarly journals Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production

1995 ◽  
Vol 48 (4) ◽  
pp. 1272-1277 ◽  
Author(s):  
Tamás Sütő ◽  
György Losonczy ◽  
Changbin Qiu ◽  
Cheryl Hill ◽  
Lennie Samsell ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
No Production ◽  
Acute Changes ◽  
Nitrite Nitrate ◽  
Renal Vascular

scholarly journals Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

2008 ◽  
Vol 54 (2) ◽  
pp. 292-300 ◽  
Author(s):  
Renke Maas ◽  
Edzard Schwedhelm ◽  
Lydia Kahl ◽  
Huige Li ◽  
Ralf Benndorf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Urinary Excretion ◽  
Indirect Evidence ◽  
No Oxidation ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Synthesis Rate ◽  
No Production

Abstract Background: Endothelial function is impaired in hypercholesterolemia and atherosclerosis. Based on mostly indirect evidence, this impairment is attributed to reduced synthesis or impaired biological activity of endothelium-derived nitric oxide (NO). It was the aim of this study to directly estimate and compare whole-body NO production in normo- and hypercholesterolemia by applying a nonradioactive stable isotope dilution technique in vivo. Methods: We enrolled 12 normocholesterolemic and 24 hypercholesterolemic volunteers who were all clinically healthy. To assess whole-body NO synthesis, we intravenously administered l-[guanidino-(15N2)]-arginine and determined the urinary excretion of 15N-labeled nitrate, the specific end product of NO oxidation in humans, by use of gas chromatography-mass spectrometry. In addition, we measured flow-mediated vasodilation (FMD) of the brachial artery, expression of endothelial NOS (eNOS) in platelets, plasma concentration of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), and urinary excretion of 8-isoprostaglandin F2α (8-iso-PGF2α). Results: After infusion of l-[guanidino-(15N2)]-arginine, cumulative excretion of 15N-labeled-nitrate during 48 h was 40% [95% CI 15%–66%] lower in hypercholesterolemic than normocholesterolemic volunteers [mean 9.2 (SE 0.8) μmol vs 15.4 (2.3) μmol/l, P = 0.003]. FMD was on average 36% [4%–67%] lower in hypercholesterolemic than normocholesterolemic volunteers [6.3 (4.0)% vs 9.4 (4.6)%, P = 0.027]. Normalized expression of NOS protein in platelets was also significantly lower in hypercholesterolemic volunteers, whereas there were no significant differences in plasma ADMA concentration or urinary excretion of 8-iso-PGF2α between the 2 groups. Conclusions: This study provides direct evidence for a decreased whole body NO synthesis rate in healthy people with hypercholesterolemia.

scholarly journals Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

2009 ◽  
Vol 297 (6) ◽  
pp. F1606-F1613 ◽  
Author(s):  
Libor Kopkan ◽  
Md Abdul H. Khan ◽  
Agnieszka Lis ◽  
Mouhamed S. Awayda ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Sodium Reabsorption ◽  
No Production ◽  
Sprague Dawley ◽  
Appreciable Change ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Renal Responses

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 μg·min−1·100 g body wt−1; bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats ( n = 8), cholesterol induced reductions of 10 ± 2% in RBF [baseline (b) 7.6 ± 0.3 μg·min−1·100 g−1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 μg·min−1·100 g−1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 μmol·min−1·100 g−1) and 24 ± 2% in nitrite/nitrate excretion (b, 0.22 ± 0.01 nmol·min−1·100 g−1) without an appreciable change in GFR (b, 0.87 ± 0.03 ml·min−1·100 g−1). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 μg·min−1·100 g−1; n = 6). In rats pretreated with superoxide (O2−) scavenger tempol (50 μg·min−1·100 g−1; n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 μg·min−1·100 g−1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 μg·min−1·100 g−1; n = 5), indicating that Na+/K+/2Cl− cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na+/K+/2Cl− cotransporter.

scholarly journals Dietary Nitrite: from menace to marvel

2016 ◽  
Vol 6 (11) ◽  
pp. 691 ◽  
Author(s):  
Nathan S. Bryan
Keyword(s):  
Nitric Oxide ◽  
Health Benefits ◽  
Biomedical Science ◽  
No Production ◽  
Positive Health ◽  
Therapeutic Benefits ◽  
Rigorous Research ◽  
Science Community ◽  
Nitrite Nitrate ◽  
Nutrition Epidemiology

Background: There are now indisputable health benefits of nitrite when administered in a clinical setting for specific diseases.  Most of the published reports identify the production of nitric oxide (NO) as the mechanism of action for nitrite.  Basic science as well as clinical studies demonstrates nitrite and/or nitrate can restore NO homeostasis as an endothelium independent source of NO that may be a redundant system for endogenous NO production.  Nitrate must first be reduced to nitrite by oral commensal bacteria and then nitrite further reduced to NO along the physiological oxygen gradient.  Despite decades of rigorous research on its safety and efficacy as a curing agent, sodium nitrite is still regarded by many as a toxic undesirable food additive.  However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide insufficiency.  This review will highlight the fundamental biochemistry of nitrite and nitrate in human physiology and provide evidence that nitrite and nitrate be considered essential nutrients.  Foods or diets enriched with nitrite can have profound positive health benefits. Keywords: nitrite, nitrate, nitric oxide, curing, nutrition, epidemiology, cardiovascular, cancer, diet, nitrosamines, antioxidants

scholarly journals Basal and stimulated nitric oxide in control of kidney function in the aging rat

1997 ◽  
Vol 272 (6) ◽  
pp. R1747-R1753 ◽  
Author(s):  
C. Hill ◽  
A. M. Lateef ◽  
K. Engels ◽  
L. Samsell ◽  
C. Baylis
Keyword(s):  
Nitric Oxide ◽  
Vascular Resistance ◽  
Pressor Response ◽  
Renal Vascular Resistance ◽  
Oxidation Products ◽  
No Oxidation ◽  
No Production ◽  
Sprague Dawley ◽  
Vasoconstrictor Response ◽  
Renal Vascular

To investigate the activity of nitric oxide (NO) in control of renal hemodynamics during aging, studies were conducted on conscious Sprague-Dawley rats aged 3-5 mo (young, Y) and 18-22 mo (old, O). Blood pressure (BP) and renal vascular resistance (RVR) were higher in O vs. Y in control, and acute systemic NO synthesis inhibition (NOSI) increased BP and RVR, with an enhanced renal vasoconstrictor response in O. Infusion of the NO substrate L-arginine produced similar, selective renal vasodilation in both groups. The endothelium-dependent vasodilator acetylcholine caused similar falls in BP and RVR, whereas sodium nitroprusside produced an exaggerated depressor response in O vs. Y without falls in RVR in either age group. Urinary excretion of the stable NO oxidation products (NOx) decreased with age, suggesting a decline in the overall somatic NO production. In conclusion, basal tonically produced NO has a more pronounced role in maintenance of renal perfusion in aging, whereas L-arginine- and agonist-stimulated renal vasodilation is not impaired with age. NO production from some source may be reduced with aging, as indicated by falls in 24-h NOX excretion, although the similarity in pressor response and enhanced renal vasoconstrictor response to NOSI suggests that the role of NO in control of total peripheral and renal vascular resistance is maintained.

Age-related changes in renal hemodynamics in female rats: role of multiple pregnancy and NO

1997 ◽  
Vol 272 (6) ◽  
pp. R1985-R1989 ◽  
Author(s):  
J. F. Reckelhoff
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Multiple Pregnancy ◽  
Renal Hemodynamics ◽  
Female Rats ◽  
No Production ◽  
Renal Vasculature ◽  
Pregnant Rats ◽  
Age Related ◽  
Renal Vascular

The objective of the present study was to evaluate 1) the effect of multiple pregnancy and aging on renal function and 2) the effect of NO inhibition on renal function in aged virgin and multiply pregnant rats. Renal hemodynamics were measured in the presence or absence of chronic (2 wk) NO synthase inhibition (nitro-L-arginine methyl ester, L-NAME) in young virgins (YV, 3-4 mo), old virgins (OV, 17-18 mo), and old retired breeders (ORB, 17-18 mo) that had sustained eight to nine pregnancies and lactations. Blood pressure was not different between control YV and OV. Glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR) were similar in OV and control YV. In contrast, the renal vasculature of ORB was more vasoconstricted in ORB than in YV or OV:GFR was decreased by 35% and RVR was higher than in YV or OV. With L-NAME there were similar increases in arterial pressure in all rats. In control YV, L-NAME had no effect on GFR, decreased RPF by 20%, and increased RVR by twofold. In OV, L-NAME decreased GFR by 30% and RPF by 60% and increased RVR by 3.3-fold. In ORB, L-NAME had no effect on GFR, decreased RPF by 30%, and increased RVR by 1.8-fold. These data suggest that the renal vasculature of ORB is vasoconstricted and that the mechanism may be due to a decrease in NO production.

Oxoproline kinetics and oxoproline urinary excretion during glycine- or sulfur amino acid-free diets in humans

2000 ◽  
Vol 278 (5) ◽  
pp. E868-E876 ◽  
Author(s):  
Cornelia C. Metges ◽  
Yong-Ming Yu ◽  
Wei Cai ◽  
Xiao-Ming Lu ◽  
Sue Wong ◽  
...  
Keyword(s):  
Amino Acid ◽  
Urinary Excretion ◽  
Control Diet ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Sulfur Amino Acid ◽  
Oxidation Rates ◽  
Acute Changes ◽  
Kinetics Of ◽  
Control Study

l-5-oxoproline (l-5-OP) is an intermediate in glutathione synthesis, possibly limited by cysteine availability. Urinary 5-OP excretion has been proposed as a measure of glycine availability. We investigated whether 5 days of dietary sulfur amino acid (SAA-free) or glycine (Gly-free) restriction affects plasma kinetics of 5-OP and urinary excretion of l- andd-5-OP in 6 healthy men. On day 6, l-5-[1-13C]oxoproline and [3,3-2H2]cysteine were infused intravenously for 8 h (3 h fast/5 h fed). In a control study (adequate amino acid mixture), plasma oxoproline fluxes were 37.8 ± 13.8 (SD) and 38.4 ± 14.8 μmol ⋅ kg−1⋅ h−1; oxidation accounted for 85% of flux. Cysteine flux was 47.9 ± 8.5 and 43.2 ± 8.5 μmol ⋅ kg−1⋅ h−1for fast and fed phases, respectively. Urinary excretion ofl- and d-5-OP was 70 ± 34 and 31.1 ± 13.3 μmol/mmol creatinine, respectively, during days 3–5, and 46.4 ± 13.9 and 22.4 ± 8.3 μmol/mmol over the 8-h tracer study. The 5-OP flux for the Gly-free diet was higher ( P = 0.018) and tended to be higher for the SAA-free diet ( P = 0.057) when compared with the control diet. Oxidation rates were higher on the Gly-free ( P = 0.005) and SAA-free ( P = 0.03) diets. Cysteine fluxes were lower on the the Gly-free ( P= 0.01) and the SAA-free diets ( P = 0.001) compared with the control diet. Rates of l-5-OP excretion were unchanged by withdrawal of SAA or Gly for 5 days but increased on day 6( P = 0.005 and P = 0.019, respectively). Thus acute changes in the dietary availability of SAA and Gly alter oxoproline kinetics and urinary 5-OP excretion.

Nitric oxide synthesis by rat pleural mesothelial cells: induction by cytokines and lipopolysaccharide

1993 ◽  
Vol 265 (2) ◽  
pp. L110-L116 ◽  
Author(s):  
M. W. Owens ◽  
M. B. Grisham
Keyword(s):  
Nitric Oxide ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
No Production ◽  
Nitrate Accumulation ◽  
Pleural Mesothelial Cells ◽  
Nitrate Production ◽  
Close Proximity ◽  
Nitrite Nitrate

The close proximity of pleural mesothelial cells (PMC) and mononuclear cells during pleural inflammation suggests that leukocyte-derived products (e.g., cytokines) may play an important role in modulating PMC function. The purpose of this study was to determine whether certain cytokines and bacterial products induce PMC to produce nitric oxide (NO). Confluent monolayers of rat PMC were exposed to tumor necrosis factor (TNF), interleukin-1 beta (IL-1), gamma-interferon (IFN), or lipopolysaccharide (LPS) individually and in various double and triple combinations for 6–72 h. Concentrations of nitrite and nitrate were quantified and used as indirect indices of NO production. Nitrite/nitrate accumulation was maximal at 72 h, with most of the increase occurring from 48 to 72 h. Maximal nitrite/nitrate production was observed with triple combinations with the combination of LPS, IL-1, and TNF giving the highest concentration (137.4 +/- 2.8 microM). Nitrite/nitrate production was significantly inhibited by NG-nitro-L-arginine methyl ester, suggesting that nitrite and nitrate were derived from the L-arginine-dependent formation of NO. These data indicate that PMC can be induced to produce large amounts of NO in response to specific combinations of proinflammatory cytokines and LPS.

Role of nitric oxide in airway remodelling

2000 ◽  
Vol 98 (3) ◽  
pp. 291-294 ◽  
Author(s):  
Esteban C. GABAZZA ◽  
Osamu TAGUCHI ◽  
Shigenori TAMAKI ◽  
Shuichi MURASHIMA ◽  
Hiroyasu KOBAYASHI ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Causative Factor ◽  
Wall Thickening ◽  
No Production ◽  
Airway Remodelling ◽  
Pathophysiological Mechanism ◽  
Airway Wall ◽  
High Resolution Computed Tomography ◽  
Bronchial Wall ◽  
Nitrite Nitrate

Airway remodelling, which is manifested by thickening of bronchial wall, is an important causative factor of bronchial hyper-responsiveness in asthma. The pathophysiological mechanism of airway remodelling is not clear. In the present study we evaluated the relationship between nitric oxide (NO) generation and airway wall thickening in patients with chronic asthma. As a marker of NO production, the levels of nitrite/nitrate were measured in induced sputum, and bronchial wall thickening was measured by high-resolution computed tomography. Sputum concentrations of nitrite/nitrate were significantly increased in asthmatic patients compared with controls. The ratio of airway wall thickness to lumen diameter was significantly correlated with the sputum concentration of nitrite/nitrate. Although statistical correlation does not prove causation, this finding suggests that NO may play a key role in the pathogenesis of airway remodelling.

Role of erythropoietin and nitric oxide in modulating the tone of human renal interlobular and subcutaneous arteries from uraemic subjects

1999 ◽  
Vol 97 (6) ◽  
pp. 639-647 ◽  
Author(s):  
Xiao Chun WU ◽  
Nicholas T. RICHARDS ◽  
Edward J. JOHNS
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Methyl Ester ◽  
Vascular Resistance ◽  
No Production ◽  
Resting Tension ◽  
Acute Responses ◽  
Resting Tone ◽  
Renal Vascular

This study investigated potential reasons why erythropoietin (EPO) given therapeutically to patients with renal failure may increase peripheral, but not renal, vascular resistance. This was done by comparing the effects of EPO on resting tension in normal renal interlobular and subcutaneous vessels from uraemic patients. In human subcutaneous arteries from uraemic subjects, noradrenaline- and KCl-induced vasoconstrictions were enhanced when nitric oxide (NO) production was blocked with NG-nitro-L-arginine methyl ester (L-NAME), but were unaffected by EPO, while acetylcholine- and bradykinin-induced concentration-dependent relaxations were markedly attenuated by L-NAME, but not by EPO. The noradrenaline- and KCl-induced vasoconstrictions of human renal interlobular arteries were unaffected by the presence of L-NAME, but were attenuated by EPO (20 units·ml-1) by some 33% (P< 0.01); this effect was enhanced by the co-administration of L-NAME. Acetylcholine and bradykinin caused comparable dilatations of the interlobular arteries; the response to the former was attenuated by L-NAME, but none of these responses were changed by EPO. EPO given alone, at a concentration of either 0.1 or 20 units·ml-1, had no effect on basal resting tone. NO production mediated both acetylcholine- and bradykinin-induced relaxation in this vessel type. In contrast, in the interlobular arteries there was no indication of NO modulating the level of vasoconstriction, and it only mediated acetylcholine-induced dilation. These acute responses to EPO only partially explain its differential effects on the vasculature in renal failure.

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