***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: There is indirect evidence for a gender difference in nitric oxide ( NO ) synthesis from vascular endothelium . The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-[15N]2-guanidino arginine .  Twenty-four healthy volunteers ( 13 men aged 22 to 40 years and 11 women aged 23 to 42 years ) participated in this study . No subjects were receiving any medication . Women were studied between the 7th and 14th days of their menstrual cycles .  Arterial blood pressure was measured oscillometrically , and 1.13 micromol L-[15N]2 arginine was administered intravenously after an overnight fast . Urine was collected for the next 36 hours in separate 12-hour periods . Urinary 15N/14N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer . Mean 36-hour urinary 15N nitrate excretion was greater in women than in men ( 2111+/-139 versus 1682+/-87 etamol ; P<0.05 ) . Furthermore , total urinary 15N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects ( coefficient of correlation , 0.47 ; P=0.022 ) . The present data show that whole-body production of NO is greater in healthy premenopausal women than in men under ambulatory conditions . The cellular origin of NO measured in this study is unknown , but differences in endothelial production could underlie differences in vascular function between men and women & NA ; Current methods for assessing vasomotor endothelial function are impractical for use in large studies . We tested the hypothesis that pulse‐wave analysis ( PWA ) combined with provocative pharmacological testing might provide an alternative method . Radial artery waveforms were recorded and augmentation index ( AIx ) was calculated from derived aortic waveforms . Thirteen subjects received  sublingual nitroglycerin ( NTG ) , inhaled albuterol , or placebo . Twelve subjects received NTG , albuterol , and placebo separately during an infusion of NG‐monomethyl‐L‐arginine ( LNMMA ) or norepinephrine . Twenty‐seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol .  Endothelial function was assessed by PWA and forearm blood flow in 27 subjects .  Albuterol and NTG both significantly and repeatably reduced AIx ( P<0.001 ) . Only the response to  albuterol was inhibited by LNMMA ( −9.8±5.5 % vs −4.7±2.7 % ; P=0.02 ) . Baseline AIx was higher in the hypercholesterolemic subjects , who exhibited a reduced response to albuterol ( P=0.02 ) but not to NTG when compared with matched controls . The responses to albuterol and acetylcholine were correlated ( r=0.5 , P= 0.02 ) . Consistent with an endothelium‐dependent effect , the response to albuterol was substantially inhibited by LNMMA . Importantly , the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra‐arterial acetylcholine . This methodology provides a simple , repeatable , noninvasive means of assessing endothelial function in vivo We investigated the effects of a high dietary supplement of arginine on plasma arginine , ornithine , and leucine kinetics and on urea production and excretion in five healthy young adult men . Subjects received either 56 or 561 mg arginine.kg-1.day-1 for 6 days via a complete L-amino acid diet , and on day 7 a tracer protocol ( first 3 h fasted ; next 5 h fed ) was conducted , involving primed constant intragastric infusions of L-[15N2-guanidino,5,5 - 2H2]arginine , L-[5 - 13C]ornithine , L-[5,5,5 - 2H3]leucine , and [15N2]urea , with a prime of H13CO3 .  Plasma arginine and ornithine fluxes increased significantly ( P < 0.05 ) with arginine supplementation , as did the rate of conversion of plasma labeled arginine to ornithine ( P < 0.05 ) and rate of ornithine oxidation ( P < 0.001 ) . However , absolute changes in ornithine kinetics were less than those for arginine or those based on changes expected from the change in arginine intake , implying a complex compartmentation in both whole body arginine and ornithine metabolism . The plasma NO3 concentration , daily output of total NO3 , and conversion of [15N]arginine to NO3 did not differ between the diets . Urea production and excretion were reduced significantly with arginine supplementation , suggesting an anabolic effect on the whole body nitrogen economy , possibly via the raised plasma insulin levels ( P = 0.013 ) during the pr and ial phase OBJECTIVE A reduced bioactivity of endothelial nitric oxide ( NO ) has been implicated in the pathogenesis of atherosclerosis . In humans , the endothelial L-arginine-NO pathway has been indirectly assessed via the flow response to endothelium-dependent vasodilators locally administered into the coronary , pulmonary or forearm circulation . However , biochemical quantification of endothelial NO formation in these organ circulations has been hampered so far because of the rapid metabolism of NO . Therefore , we aim ed to work out a reliable biochemical index to assess endothelial NO formation in human circulation . METHODS In 33 healthy volunteers ,  forearm blood flow ( FBF )  was measured by st and ard techniques of venous occlusion plethysmography at rest , after local application of the endothelium-dependent vasodilator acetylcholine ( ACH ) , the endothelium-independent vasodilator papaverine ( PAP ) , the stereospecific inhibitor of endothelial NO synthase ( eNOS ) L-NMMA , and L-arginine ( ARG ) , the natural substrate of eNOS . In parallel , nitrite and nitrate concentrations in blood sample s taken from the antecubital vein were measured by HPLC using anion-exchange chromatography in combination with electrochemical and ultraviolet detection following a specific sample preparation method . RESULTS ACH dose-dependently increased resting FBF ( from 3.0 + /- 0.3 to 10.4 + /- 0.9 ml/min per 100 ml tissue ) and serum nitrite concentration ( from 402 + /- 59 to 977 + /- 82 nmol/l , both p < 0.05 , n = 12 ) . A significant correlation was observed between the changes in FBF and the serum nitrite concentration ( r = 0.61 , p < 0.0001 ) . L-NMMA reduced resting FBF and endothelium-dependent vasodilation by 30 % and this was paralleled by a significant reduction in serum nitrite concentration at the highest dose of ACH ( n = 9 , p < 0.001 ) . PAP increased FBF more than fourfold , but did not affect serum nitrite concentration ( n = 11 ) , whereas ARG significantly increased both FBF and nitrite . Basal serum nitrate amounted to 25 + /- 4 mumol/l and remained constant during the application of ACH , PAP and L-NMMA . CONCLUSIONS The concentration of serum nitrite sensitively reflects changes in endothelial NO formation in human forearm circulation . This biochemical measure may help to characterize the L-arginine-NO pathway in disease states associated with endothelial dysfunction and to further eluci date its pathophysiological significance for the development of atherosclerosis in humans In humans , the role of nitric oxide ( NO ) in host defence is controversial . We prospect ively studied plasma levels of nitrate , the stable end-product of NO formation , during acute infection in 43 patients controlled with regard to dietary nitrate/nitrite .  During acute gastroenteritis the mean plasma nitrate level was significantly increased compared with at recovery 4 - 5 weeks later ( 118 vs. 32.5 micromol/l ; p < 0.001 ) , in contrast with the findings in patients with acute pneumonia ( PN ; 34.6 vs. 42.8 micromol/l ) or febrile urinary tract infection ( UTI ; 27.7 vs. 31.3 micromol/l ) . In a second group of 20 retrospectively studied patients with severe PN or UTI , of whom 70 % were bacteraemic , no significantly increased nitrate levels could be demonstrated during the acute stage of infection . These findings indicate that increased NO production , as measured by plasma nitrate , is not a general finding in patients with acute infectious diseases , but may rather be associated with certain pathogens or sites of infection 
    Output:
    
Three protocol s were identified , including the arginine-citrulline , the arginine-nitrate , and the oxygen-nitrate protocol s. The arginine-citrulline protocol showed a wider variability compared to the arginine-nitrate and oxygen-nitrate protocol s. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder ( inflammatory , metabolic , vascular ) .
The precision of several aspects of the techniques and the validity of some assumptions made remain unknown , and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age