Simvastatin treatment increases nitrite levels in obese women: Modulation by T−786C polymorphism of eNOS

Andrade, Vanessa L.; Sertório, Jonas T.; Eleuterio, Nibia Mariana; Tanus‐Santos, José Eduardo; Fernandes, Karin Sá; Sandrim, Valéria C.

doi:10.1016/j.niox.2013.07.005

Cited by 18 publications

(13 citation statements)

References 35 publications

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“…The increased NO in the present study with simvastatin treatment in congruence with several studies reported that statins improve NO bioavailability (Ozuyaman et al, 2008;Harisa et al, 2012;Li and Forstermann, 2013;Glutkina, 2013;Andrade et al, 2013). Moreover, it has been established that atheroprotective effect of statins is mediated by restoring the normal NO/peroxynitrite balance (Heeba et al, 2009).…”

Section: Discussionsupporting

confidence: 90%

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Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Harisa¹,

Alanazi²,

Attia³

et al. 2015

International J. of Pharmacology

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A B S T R A C TThis study was undertaken to investigate the impact simvastatin chronotherapy on erythrocytes Nitric Oxide Synthase (NOS) activity. In the present study we select 24 adult human subjects have plasma total cholesterol high borderline (200-230 mg dLG 1 ). Subjects were administrated simvastatin (20 mg day time) for 2 months. Afterward, they were recommended for washout period (2 weeks), then subjects were administered the same dose at night time for additional 2 months. The present results showed that both day time and night time simvastatin treatment regimen significantly decrease plasma atherogenic index, malondialdehyde and protein carbonyl levels. However, paraoxonase-1 activity and total thiol level were significantly increased. Moreover, simvastatin therapy improved nitrite (NO marker) levels in both plasma and erythrocytes compared to baselines. As well, simvastatin day time and night time dosing significantly increased erythrocytes NOS activity (46 and 64%, respectively) compared to baselines. Night time dosing induced marked increase of NOS activity (19%) compared to day time. This study confirms that night time dosing boost hypocholesterolemic, antioxidant and NO modulating effects of simvastatin compared to day time.

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Section: Discussionsupporting

confidence: 90%

“…NO is a major player in the regulation of the cardiovascular system and reduced NO bioavailability has been linked to cardiovascular disorders (Andrade et al, 2013). The decrease of NO bioavailability associated with erythrocyte dysfunction and cardiovascular complications (Mason et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Harisa¹,

Alanazi²,

Attia³

et al. 2015

International J. of Pharmacology

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“…Multiple agents within these broad classes of medication have been shown to upregulate endothelial (e) NOS activity [42][43][44]. When the current cohort was split for drug classifications, no differences in baseline plasma nitrite were detectable.…”

Section: Placebomentioning

confidence: 99%

Effects of dietary nitrate supplementation on the oxygen cost of exercise and walking performance in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled crossover trial

Shepherd

Gilchrist

Winyard

et al. 2015

Free Radical Biology and Medicine

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Dietary nitrate supplementation has been shown to reduce the oxygen (O2) cost of exercise and enhance exercise tolerance in healthy individuals. This study assessed whether similar effects could be observed in individuals with type 2 diabetes (T2DM). In a randomized, double-blind, placebo-controlled crossover study, 48 participants with T2DM supplemented their diet for 4 days with either nitrate-rich beetroot juice (70ml/day, 6.43mmol nitrate/day) or nitrate-depleted beetroot juice as placebo (70ml/day, 0.07mmol nitrate/day). After each intervention period, resting plasma nitrate and nitrite concentrations were measured subsequent to participants completing moderate-paced walking. Pulmonary gas exchange was measured to assess the O2 cost of walking. After a rest period, participants performed the 6-min walk test (6MWT). Relative to placebo, beetroot juice resulted in a significant increase in plasma nitrate (placebo, 57±66 vs beetroot, 319±110µM; P< 0.001) and plasma nitrite concentration (placebo, 680±256 vs beetroot, 1065±607nM; P < 0.001). There were no differences between placebo juice and beetroot juice for the O2 cost of walking (946±221 vs 939±223ml/min, respectively; P = 0.59) and distance covered in the 6MWT (550±83 vs 554±90m, respectively; P = 0.17). Nitrate supplementation did not affect the O2 cost of moderate-paced walking or improve performance in the 6MWT. These findings indicate that dietary nitrate supplementation does not modulate the response to exercise in individuals with T2DM.

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“…The CC genotype was also associated with reduction of plasma sCD40-L, sVCAM, sP-selectin and MMP-9 in response to atorvastatin, in health men (Souza-Costa et al, 2007). NOS3 -786C allele was also associated with the increase in blood nitrite but not with the reduction of plasma malondialdehyde in obese women treated with simvastatin (Andrade et al, 2013).…”

Section: Endothelial Function-related Genesmentioning

confidence: 87%

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

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Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

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Simvastatin treatment increases nitrite levels in obese women: Modulation by T−786C polymorphism of eNOS

Abstract: Our results demonstrated a restoration of nitrite levels in obese women treated with simvastatin, which is modulated by T(-786)C polymorphism.

Cited by 18 publications

References 35 publications

Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Effects of dietary nitrate supplementation on the oxygen cost of exercise and walking performance in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled crossover trial

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

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