***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Recent studies surprisingly show that dietary inorganic nitrate , abundant in vegetables , can be metabolized in vivo to form nitrite and then bioactive nitric oxide . A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate ;  an effect consistent with formation of vasodilatory nitric oxide . Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite . In a cross-over design ed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate ( 10mg/kg dissolved in water ) . In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load . Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite . We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria . The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate Nitric Oxide ( NO ) bioavailability is essential for vascular health . Dietary supplementation with inorganic nitrate , which is abundant in vegetables and roots , has been identified as an effective means of increasing vascular NO bioavailability . Recent studies have shown a reduction in resting blood pressures in both normotensive and hypertensive subjects following ingestion of inorganic nitrate . Oral bacteria play a key role in this process and the use of strong antibacterial mouthwash rinses can disable this mechanism . Hence , mouthwash usage , a $ 1.4 billion market in the US , may potentially be detrimental to cardiovascular health . The purpose of this study was to examine the effects of different strengths of commercially available mouthwash products on salivary and plasma nitrate and nitrite concentrations following 8.4 mmol inorganic nitrate load ( beetroot juice ) . Specifically , we examined the effects of Listerine antiseptic mouthwash , Cepacol antibacterial mouthwash , and Chlorhexidine mouthwash versus control ( water ) .  Twelve apparently healthy normotensive males ( 36 ± 11 yrs ) completed four testing visits in a r and omized order , separated by one week . Testing consisted of blood pressure ( BP ) , and saliva and venous blood collection at baseline and each hour for 4 h. Following baseline-testing participants consumed 140 ml of beet juice and then 15 min later gargled with 5 mL of assigned mouthwash . Testing and mouthwash rinse was repeated every hour for 4 h. Linear mixed effects models , followed by pairwise comparisons where appropriate , were used to determine the influence of treatment and time on plasma and saliva nitrate and nitrite , and BP . Plasma and salivary nitrate increased above baseline ( time effect ) for all conditions ( p ≤ 0.01 ) . There were time ( p ≤ 0.01 ) , treatment ( p ≤ 0.01 ) , and interaction ( p ≤ 0.05 ) effects for plasma and salivary nitrite . There was a treatment effect on systolic BP ( p ≤ 0.05 ) . Further examination revealed a differentiation of plasma and salivary nitrite concentration  between control/antiseptic and antibacterial/chlorhexidine treatments . When examined in this manner there was a reduction in both SBP ( p ≤ 0.01 ) and mean arterial BP ( p ≤ 0.05 ) from the antibacterial/chlorhexidine treatments . These results suggest a potentially differentiating effect of different commercially available mouthwash solutions on plasma and salivary nitrite concentrations and resting blood pressure responses . This raises potential public health related questions on the appropriate widespread usage of different mouthwash formulations Circulating nitrate ( NO3− ) , derived from dietary sources or endogenous nitric oxide production , is extracted from blood by the salivary gl and s , accumulates in saliva , and is then reduced to nitrite ( NO2− ) by the oral microflora . This process has historically been viewed as harmful , because nitrite can promote formation of potentially carcinogenic N-nitrosamines . More recent research , however , suggests that nitrite can also serve as a precursor for systemic generation of vasodilatory nitric oxide , and exogenous administration of nitrate reduces blood pressure in humans . However , whether oral nitrate-reducing bacteria participate in “ setting ” blood pressure is unknown . We investigated whether suppression of the oral microflora affects systemic nitrite levels and hence blood pressure in healthy individuals . We measured blood pressure ( clinic , home , and 24-h ambulatory ) in 19 healthy volunteers during an initial 7-day control period followed by a 7-day treatment period with a chlorhexidine-based antiseptic mouthwash . Oral nitrate-reducing capacity and nitrite levels were measured after each study period . Antiseptic mouthwash treatment reduced oral nitrite production by 90 % ( p < 0.001 ) and plasma nitrite levels by 25 % ( p = 0.001 ) compared to the control period . Systolic and diastolic blood pressure increased by 2–3 .5 mm Hg , increases correlated to a decrease in circulating nitrite concentrations ( r2 = 0.56 , p = 0.002 ) . The blood pressure effect appeared within 1 day of disruption of the oral microflora and was sustained during the 7-day mouthwash intervention . These results suggest that the recycling of endogenous nitrate by oral bacteria plays an important role in determination of plasma nitrite levels and thereby in the physiological control of blood pressure BACKGROUND Endothelial nitric oxide ( NO ) is fundamental to cardiovascular health . Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate-nitrite-NO pathway . A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota . We aim ed to assess the effects of antibacterial mouthwash use on markers of nitrate-nitrite-NO metabolism and blood pressure in treated hypertensive men and women . METHODS Fifteen treated hypertensive men and women ( mean age 65 years ) were recruited to a r and omized controlled cross-over trial . The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction , salivary and plasma nitrate and nitrite , plasma cyclic guanosine monophosphate ( cGMP ) and systolic and diastolic blood pressure were compared to control ( water ) . RESULTS Relative to control , 3-day antibacterial mouthwash use result ed in decreased oral nitrate to nitrite reduction ( P = 0.02 ) , decreased salivary nitrite ( P = 0.01 ) and increased salivary nitrate ( P < 0.001 ) , and there was a trend toward a decrease in plasma nitrite concentration ( P = 0.09 ) . Use of antibacterial mouthwash over 3 days also result ed in higher systolic blood pressure ( 2.3 mm Hg ; 95 % CI : 0.5 , 4.0 ; P = 0.01 ) , but not diastolic blood pressure ( P = 0.4 ) or plasma cGMP ( P = 0.7 ) , relative to control . CONCLUSIONS Interruption of the nitrate-nitrite-NO pathway through the use of antibacterial mouthwash was paralleled by a small elevation of systolic blood pressure in treated hypertensive men and women Background : The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content . Objective : We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate ( nitrate-rich beetroot juice ) compared with placebo intake ( nitrate-depleted beetroot juice ) on vascular and platelet function in untreated hypercholesterolemics . Design : A total of 69 subjects were recruited in this r and omized , double-blind , placebo-controlled parallel study . The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation ( FMD ) . Results : Baseline characteristics were similar between the groups , with primary outcome data available for 67 patients . Dietary nitrate result ed in an absolute increase in the FMD response of 1.1 % ( an ∼24 % improvement from baseline ) with a worsening of 0.3 % in the placebo group ( P < 0.001 ) . A small improvement in the aortic pulse wave velocity ( i.e. , a decrease of 0.22 m/s ; 95 % CI : −0.4 , −0.3 m/s ) was evident in the nitrate group , showing a trend ( P = 0.06 ) to improvement in comparison with the placebo group . Dietary nitrate also caused a small but significant reduction ( 7.6 % ) in platelet-monocyte aggregates compared with an increase of 10.1 % in the placebo group ( P = 0.004 ) , with statistically significant reductions in stimulated ( ex vivo ) P-selectin expression compared with the placebo group ( P < 0.05 ) but no significant changes in unstimulated expression . No adverse effects of dietary nitrate were detected . The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment ( P < 0.01 ) . The proportions of 78 bacterial taxa were different after the nitrate treatment ; of those taxa present , 2 taxa were responsible for > 1 % of this change , with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens ( P < 0.01 ) increased after nitrate treatment relative to after placebo treatment . Conclusions : Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients . These changes are associated with alterations in the oral microbiome and , in particular , nitrate-reducing genera . Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts . This trial was registered at clinical trials.gov as NCT01493752 Abstract Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of an alternative mammalian pathway to produce nitric oxide in humans . Preliminary evidence suggests important sex differences in this pathway . We prospect ively investigated sex‐differences following inorganic nitrate supplementation on nitrate/nitrite levels and vascular function , and separately examined sex differences in oral nitrate reduction , and oral microbiota by 16S rRNA profiling . At baseline , females exhibit higher nitrite levels in all biological matrices despite similar nitrate levels to males . Following inorganic nitrate supplementation , plasma nitrite was increased to a significantly greater extent in females than in males and pulse wave velocity was only reduced in females . Females exhibited higher oral bacterial nitrate‐reducing activity at baseline and after nitrate supplementation . Despite these differences , there were no differences in the composition of either the total salivary microbiota or those oral taxa with nitrate reductase genes . Our results demonstrate that females have augmented oral nitrate reduction that contributes to higher nitrite levels at baseline and also after inorganic nitrate supplementation , however this was not associated with differences in microbial composition ( clinical trials.gov : NCT01583803 ) . Graphical abstract Figure . No caption available . HighlightsSex differences are apparent in nitrate‐nitrite‐nitric oxide pathway under basal conditions . Females have higher nitrite levels at baseline and after nitrate supplementation . Nitrate reduction to nitrite is dependent on oral microbiota . Females have greater oral nitrate reduction capability . This difference is not due to differences in oral microbiome community composition 
    Output:
    
Conclusions : Although , the role of oral bacteria has been unequivocally demonstrated in the regulation of salivary NO 3 - metabolism , their influence on plasma concentration of NO species remains ambiguous .