Significance of Inorganic Nitrate Supplement in Cardiovascular Health

Author(s):  
Rupesh Dudhe ◽  
Anshu Chaudhary Dudhe ◽  
Shravan D. Raut

Background amp; Objectives: Nitric Oxide (NO) is frequently produced by the enzyme Nitric Oxide Synthase (NOS) and is crucial to the control and effective ness of the cardiovascular system. However, there is substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular obstacles. Fortunately, NO can also being produced by sequential reduction of inorganic nitrates supplementation. This proves that NO from inorganic nitrate supplements can provide compensation when NOS activity is inadequate and cardio protective benefits and beyond that provided by healthy NOS system. Discussion: This review focus on the general information about Nitrous oxide, types, mechanism of action of NO & overview of NOS activity is inadequate and cardio protective benefits and beyond that provided by healthy NOS system were often studied for cardiovascular treatments. Conclusion: We concluded that the Natural plant NO is the essential for cardiovascular activity to target site with desired concentration. Moreover, the researchers were focused on Evidence suggested that nitrate supplementation can help regulate blood pressure, limit progression of atherosclerosis, and improve myocardial contractility in both healthy individuals and those with cardiovascular disease.

2016 ◽  
Vol 14 (1) ◽  
pp. 78-88
Author(s):  
Alexander S Radchenko

The The last two decades there has been a growing interest in the nitric oxide (NO) function in the body of a healthy person. In the study, two very specific problems are discussed: a) the NO involvement in mechanisms of adaptation at muscular work under hypoxia conditions, and b) the inorganic nitrate supplementation in athlete’s diet with the aim of sports performance improvement. The reorganizations that occur in the heart vasculature and in skeletal muscle for providing muscle work under hypoxia conditions examined. The named problems are particularly relevant in contemporary sports in which the adding of hypoxic exposure on a body of training persons as well as the inorganic nitrate in sports nutrition application as added means to special performance improvement. Raise the problem of the hypoxia and inorganic nitrate mutual exploitation in the training process.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Christa Zollbrecht ◽  
Marcelo Montenegro ◽  
Michael Hezel ◽  
Eddie Weitzberg ◽  
...  

Xanthine oxidoreductase (XOR) is generally known as a source of superoxide production, but this enzyme has also been suggested to mediate NO production via reduction of inorganic nitrate (NO 3 - ) and nitrite(NO 2 - ). This pathway for NO generation is of particular importance during certain pathologies, whereas endothelial NO synthase (eNOS) is the primary source of vascular NO generation under normal physiological conditions. The exact interplay between the NOS and XOR-derived NO is not yet fully elucidated. The aim of the present study was to investigate if eNOS deficiency is partly compensated by XOR upregulation and sensitization of the NO 3 - - NO 2 - - NO pathway. NO 3 - and NO 2 - were similar between naïve eNOS KO and wildtype (wt) mice, but reduced upon chronic treatment with the non-selective NOS inhibitor L-NAME (wt: 25.0±5.2, eNOS KO: 39.2±6.4, L-NAME: 8.2±1.6 μ NO 3 - -, wt: 0.38±0.07, eNOS KO: 0.42±0.04, L-NAME: 0.12±0.02 μ NO 2 - ). XOR function was upregulated in eNOS KO compared with wt mice [(mRNA: wt 1±0.07, eNOS KO 1.38±0.17), (activity: wt 825±54, eNOS KO 1327±280 CLU/mg/min), (uric acid: wt 32.87±1.53, eNOS KO 43.23±3.54 μ)]. None of these markers of XOR activity was increased in nNOS KO and iNOS KO mice. Following acute dose of NO 3 - (10 mg/kg bw, i.p.), the increase of plasma NO 2 - was more pronounced in eNOS KO (+0.51±0.13 μ) compared with wt (+0.22±0.09 μ), and this augmented response in the eNOS KO was abolished by treatment with the highly selective XOR inhibitor febuxostat (FEB). Liver from eNOS KO had higher reducing capacity of NO 2 - to NO compared with wt, and this effect was attenuated by FEB (Δppb of NO: wt +8.7±4.2, eNOS KO +44.2±15.0, wt+FEB +22.2±9.6, eNOS KO+FEB +26.8±10.2). Treatment with FEB increased blood pressure in eNOS KO (ΔMAP:+10.2±5.6 mmHg), but had no effect in wt (ΔMAP:-0.6±3.3 mmHg). Supplementation with NO 3 - (10 mM, drinking water) reduced blood pressure in eNOS KO (ΔMAP: -6.3±2.2 mmHg), and this effect was abolished by FEB (ΔMAP: +1.1±1.9 mmHg). In conclusion, upregulated and altered XOR function in conditions with eNOS deficiency can facilitate the NO 3 - - NO 2 - - NO pathway and hence play a significant role in vascular NO homeostasis.


Author(s):  
Joshua M. Bock ◽  
Brady E. Hanson ◽  
Thomas F. Asama ◽  
Andrew J. Feider ◽  
Satoshi Hanada ◽  
...  

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53±10years, 29.2±5.8kg/m2, apnea-hypopnea index=17.8±8.1, 43%F) completed three visits. Resting brachial blood pressure, as well as cardiopulmonary responses to inspiratory hypoxia, were measured before, and two hours after, acute inorganic nitrate supplementation (~0.10mmol [placebo], 4.03mmol [low-dose], and 8.06mmol [high-dose]). Placebo did not increase either plasma [nitrate] (30±52 to 52±23μM, P=0.26) or [nitrite] (266±153 to 277±164nM, P=0.21); however, both increased following low-(29±17 to 175±42μM, 220±137 to 514±352nM) and high-doses (26±11 to 292±90μM, 248±155 to 738±427nM, respectively, P<0.01 for all). Following placebo, systolic blood pressure increased (120±9 to128±10mmHg, P<0.05) whereas no changes were observed following low-(121±11 to 123±8mmHg, P=0.19) or high-dose (124±13 to 124±9mmHg, P=0.96). The peak ventilatory response to hypoxia increased following placebo (3.1±1.2 to 4.4±2.6L/min, P<0.01) but not low-(4.4±2.4 to 5.4±3.4L/min, P=0.11) or high-doses (4.3±2.3 to 4.8±2.7L/min, P=0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P=0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.


2004 ◽  
Vol 107 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Willem R. P. AGEMA ◽  
Moniek P. M.  de MAAT ◽  
Aeilko H. ZWINDERMAN ◽  
John J. P. KASTELEIN ◽  
Ton J. RABELINK ◽  
...  

In the present study, we sought to evaluate the role of three polymorphisms in the ecNOS (endothelial constitutive nitric oxide synthase) gene in relation to the existence, severity and progression of CAD (coronary artery disease), MI (myocardial infarction) and the occurrence of ischaemia in a predominantly Caucasian population. Patients with CAD (n=760) and age- and sex-matched population-based controls (n=691) were genotyped for the −786T/C, E/D298 and 4a/b polymorphisms. Patients were randomized to pravastatin (40 mg) or placebo. Progression of atherosclerosis was evaluated by sequential angiography. Functionality was assessed by ST segment analysis of ambulant ECGs. The E298 (P=0.003) and 4a (P=0.001) alleles were associated with CAD. Furthermore, E298 (P=0.009) and −786T (P=0.022) alleles were associated with previous MI among patients, predominantly smokers. D/D298 homozygotes, but not −786T/C or 4a/4b mutants, had longer-lasting ischaemia than others (P<0.05). We found no differences in progression of atherosclerosis, irrespective of pravastatin use. We conclude that the E/D298 polymorphism is most consistently associated with CAD, but not with progression of atherosclerosis. The E allele is associated with CAD and MI, whereas the D allele is associated with ischaemia.


2019 ◽  
Author(s):  
Michael A. Gilinsky ◽  
Yulia K. Polityko ◽  
Arkady L. Markel ◽  
Tatyana V. Latysheva ◽  
Abraham O. Samson ◽  
...  

AbstractGrowing evidence suggests that increased arginase activity affects vital bioprocesses in various systems and universally mediates the pathogenesis of numerous metabolic diseases. The adverse effects of arginase are associated with a severe decline in L-arginine bioavailability, which leads to nitric oxide synthase substrate insufficiency, uncoupling, and, eventually, to superoxide anion generation and substantial reduction of nitric oxide (NO) synthesis. In cooperation, it contributes to chronic oxidative stress and endothelial dysfunction, which might lead to hypertension and atherosclerosis.Recent preclinical investigations point to arginase as a promising therapeutic target in ameliorating metabolic and vascular dysfunctions. In the present study, adult rats with inherited stress-induced arterial hypertension (ISIAH) were used as a model of hypertension. Wistar rats served as normotensive controls. Experimental animals were intraperitoneally administered for seven days with non-proteinogenic amino acid L-norvaline (30 mg/kg/day), which is a potent arginase inhibitor, or with the vehicle. Blood pressure (BP), body weight, and diuresis were monitored. The changes in blood and urine levels of creatinine, urea, and NO metabolites were analyzed.We observed a significant decline in BP and induced diuresis in ISIAH rats following the treatment. The same procedure did not affect the BP of control animals. Remarkably, the treatment had no influence upon glomerular filtration rate in two experimental groups, just like the daily excretion of creatinine and urea. Conversely, NO metabolites levels were amplified in normotonic but not in hypertensive rats following the treatment.The data indicate that L-norvaline is a potential antihypertensive agent, and deserves to be clinically investigated. Moreover, we suggest that changes in blood and urine are causally related to the effect of L-norvaline upon the BP regulation.


Author(s):  
Muhammed Ahmed Mesaik ◽  
Almas Jabeen ◽  
Maria Saeed ◽  
Zaheer Ul-Haq ◽  
Izzaddinn Elawad Ahmed ◽  
...  

Background: Smokeless tobacco (SLT) is traditionally used in Middle East countries. The several toxic constituents with potential carcinogenicity make it a serious human health risk. Literature regarding their effects on cardiac and cancer disease is lacking in Saudi Arabia. Objective: This study was conducted to investigate the adverse effect of 11 different samples of widely used SLT varieties from the Tabuk region - Saudi Arabia, on nitric oxide (NO) level and their potential risk on cardiovascular health, etiology and/or progression of cancers. Methods: Samples were collected from Tabuk, KSA and analyzed by the GC-MS technique. Nitric oxide inhibition was performed using J774.2 macrophages by the Griess method. The retrieved crystallized structure of human inducible nitric oxide synthase (iNOS) from Brookhaven Protein Data Bank Repository PDB I.D: 3E7G with 2.20Å resolution was further prepared by structure using the MOE.2019 tool. The compounds abstracted from 11 different Shammah varieties were sketched by the MOE-Builder tool. Minimization for both receptor and compounds was performed via AMBER99 and MMFF99X force field implemented in MOE. Results: Nine samples (4 - 11) showed a potent suppressive effect on NO production with IC50 values ranging between (16.9-20.4 µg/mL), respectively. The samples (1 & 2) exhibited a moderate level of inhibition with IC50 ranging between 33.2 and 57.4 µg/mL, respectively. Interestingly, sample 4 consisting of compounds (13-15, 19-26, 28) that mostly belongs to the group fatty acid ester and phthalic acid ester showed the most potent suppressive effect. Molecular docking results revealed that the current local SLT constituents presented noticeable potency in different extract samples. Conclusion: Variable suppressive effects on NO were detected in the current SLT samples, where sample 4 was the most potent among all. The extract of the latter exhibited molecular interaction with the first shell amino acid residues of Inducible nitric oxide synthase (iNOS), which may anchor the plasticity and selectivity of the compounds present in it. The samples (4 -11) showed a potent inhibitory effect on the NO, where compound 26 (Phthalic acid ester) is common, and its adequate concentration may account for augmented biological activity. These results may effectively highlight their adverse effects on cardiovascular health and etiology and/or progression of cancer and may help in strengthening the social and governmental efforts in minimizing the use of these substances.


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