***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: Background and Purpose — There is experimental evidence that l-arginine restores diminished CO2 reactivity after mild traumatic brain injury in rats . This effect is believed to be mediated by l-arginine – derived nitric oxide , which is a permissive substrate for CO2 reactivity . To clarify whether these findings can be transferred to the clinical situation and have beneficial effects in patients , we studied the effects of l-arginine on CO2 reactivity of the cerebral vessels in patients with impaired vasomotor reactivity ( VMR ) and compared them with patients with normal VMR . Methods — Twenty-two patients with cardiovascular risk factors and VMR < 50 % with no extracranial or intracranial stenoses were examined by bilateral transcranial Doppler sonography of the right and left middle cerebral arteries  and compared with 20 age- and risk-matched patients with normal VMR ( > 50 % ) . VMR was tested by 1-minute hyperventilation , followed by a 3-minute inhalation of 5 % CO2 . Examinations were performed before and after infusion of 30 g l-arginine over 30 minutes . The 22 patients with reduced VMR ( < 50 % ) were compared with 20 patients with normal VMR ( > 50 % ) . Results — Initial mean VMR of the 42 patients was 50±12 % . There was no difference between the right- and the left-side VMR . In the 22 patients with reduced VMR in the first examination ( 42±8 % ) , VMR increased significantly after infusion of l-arginine ( 52±14 % , P = 0.005 ) . In contrast , values did not change after infusion of l-arginine in the 20 patients with normal VMR ( 59±8 % before versus 59±13 % after l-arginine ) . There was a negative correlation of initial CO2 vasoreactivity and the percentage of VMR increase after infusion of l-arginine . Conclusions — Our data support the hypothesis that in humans l-arginine is able to improve impaired CO2 reactivity of the cerebral vessels . This effect can be found in patients at cardiovascular risk with impaired VMR and might have therapeutic implication s in the future Background : It is well known that endothelial dysfunction plays an important role in the pathogenesis of many cardiovascular disorders . The aim of this study was to test the hypothesis that specific , marked endothelial dysfunction of cerebral arteries is present in patients with lacunar cerebral infa rct ions . Methods : Cerebrovascular reactivity to L-arginine , which reveals the function of the cerebral endothelium , was investigated in patients with lacunar infa rct ions ( 20 patients , 11 male and 9 female , aged 60.9 ± 7.3 years ) , 21 age- and gender-matched asymptomatic patients with similar cardiovascular risk factors ( all patients had arterial hypertension ) and 21 age- and gender-matched healthy controls .  The mean arterial velocity ( vm ) in both middle cerebral arteries was measured by transcranial Doppler sonography during a 15-min baseline period , a 30-min intravenous infusion of L-arginine and a 15-min interval after L-arginine infusion  . Arterial blood pressure , heart rate and CO2 were measured continuously . Results : The measured vm increase  during L-arginine infusion in the patients with lacunar infa rct ions ( 13.4 ± 9.1 % ) was significantly lower compared to the healthy controls ( 20.5 ± 9.9 % ) but similar to that obtained in the patients with cardiovascular risk factors ( 11.5 ± 8.9 % ) . Conclusions : Our results showed that cerebrovascular reactivity to L-arginine , which demonstrates cerebral endothelial function , is significantly impaired in patients with cardiovascular risk factors . Importantly , we found that patients with lacunar infa rct ions do not show any additional impairment of cerebral endothelial function OBJECTIVE Brain perfusion is tightly regulated over a wide range of blood pressures by local regulation of cerebral blood flow ( CBF ) . Ageing is associated with impaired CBF and impaired nitric oxide mediated vasodilator responses . The role of nitric oxide in the regulation of basal CBF in young and older subjects was investigated , using the nitric oxide synthase inhibitor L-NMMA as pharmacological tool . METHODS We used a gradient echo phase-contrast magnetic resonance imaging technique to investigate the role of nitric oxide in the regulation of cerebral blood flow in young ( 25+/-7.1 years ; n=8 ) and old ( 78+/-6.6 years ; n=7 ) volunteers . The study was performed in a double-blinded fashion and consisted of two study days . On one day the effects of the intravenously infused L-NMMA on CBF and blood pressure was measured and on the other day the effects of a matching placebo . RESULTS Basal CBF was significantly lower in old compared to young subjects ( 590+/-20 vs 704+/-20 ml/min ) , while the cerebral vascular resistance ( CVR ) levels were significantly higher ( 0.15+/-0.01 ( arbitrary units ) vs 0.12+/-0.01 , respectively ) . Infusion of L-NMMA significantly increased mean arterial pressure in both groups ( 2.8+/-1.2 mmHg ; p=0.02 in the young and in the old subjects 5.6+/-1.1 mmHg ; p<0.001 ) . Infusion of L-NMMA significantly decreased CBF ( 49+/-12 ml/min ; p<0.001 ) and increased CVR ( 0.02+/-0.004 ; p<0.001 ) in the old subjects but did not significantly influence cerebral circulation in the young subjects . CONCLUSION We conclude that compared to young subjects , in old people CBF is impaired , and dependent on the intactness of the nitric oxide pathway Background : Nitric oxide is pivotal in endothelially dependent vasodilatory regulation . An association of endothelial dysfunction with aging has been documented in the forearm and coronary vascular beds . However , the influence of aging in the human cerebral circulation , where regulation is particularly complex , is incompletely understood . Objective : We systematic ally administered L-arginine , a precursor of nitric oxide , to evaluate the influence of aging on nitric oxide-mediated cerebral vasomotor regulation . Methods : Among healthy volunteers , 20 older subjects ( 10 men , 10 women ; age : 70.2 ± 2.8 years ) and 22 younger subjects ( 10 men , 12 women ; age : 28.8 ± 1.9 years ) received intravenous infusions of L-arginine monochloride ( 500 mg/kg ) over 30 min . Hemodynamic parameters were monitored continuously during and after infusion . The cerebral vasomotor response was estimated by transcranial Doppler sonography of the right middle cerebral artery . Results : Infusion of saline as a control brought little change in the mean blood pressure , heart rate or cerebral blood flow velocity in either group . On administration of  L-arginine , cerebral blood flow velocity increased and mean blood pressure decreased . After completion of infusion , both parameters rapidly normalized . While reduction of mean blood pressure did not differ between older and younger groups , the cerebral circulation in the older group showed a blunted , smaller , and more easily saturated vasomotor response compared to the younger group , though both groups had similar baseline values . Conclusion : Our results indicate a diminished nitric oxide-mediated cerebral vasomotor response  in aging subjects . Additionally , transcranial Doppler sonography can be used to reliably evaluate age-related changes in the physiologic responses of the human cerebral circulation Objective : To assess the effects of intravenous vitamin C administration on the vasomotor responses to intracoronary l-arginine infusion in epicardial coronary arteries . Methods : 28 patients with coronary artery disease and stable angina were enrolled in the study . Eight patients received intracoronary infusions of 150 μmol/min l-arginine before and after intravenous infusion of vitamin C , 10 patients received intracoronary infusions of 150 μmol/min l-arginine before and after intravenous infusion of normal saline , and 10 patients received intracoronary normal saline before and after intravenous infusion of vitamin C. The diameter of proximal and distal coronary artery segments was measured by quantitative angiography . Results : Infusion of l-arginine caused significant dilatation of both proximal ( 4.87 (0.96)% , p < 0.01 v normal saline ) and distal ( 6.33 (1.38)% , p < 0.01 v normal saline ) coronary segments . Co-infusion of vitamin C and l-arginine  dilated proximal coronary segments by 8.68 (1.40)% ( p < 0.01 v normal saline , p < 0.01 vl-arginine ) and distal segments by 13.07 (2.15)% ( p < 0.01 v normal saline , p < 0.01 vl-arginine ) . Intravenous infusion of vitamin C caused a borderline increase in proximal and distal coronary segment diameters ( 1.93 (0.76)% and 2.09 (1.28)% , respectively , not significant ) . Conclusions : l-Arginine dependent coronary segment vasodilatation was augmented by the antioxidant vitamin C in patients with coronary artery disease .  Thus , vitamin C may have beneficial effects on nitric oxide bioavailability induced by l-arginine Objectives : L-arginine is the substrate for nitric oxide ( NO ) production and has been shown to induce an endothelium-dependent increase in cerebral blood flow in humans . We studied the hypothesis that L-arginine-mediated vasoreactivity is impaired in patients with cardiovascular risk factors and a risk of stroke . Methods : 55 patients with cardiovascular risk factors ( mean age 63.0 ± 8.5 years ) were included in the study . 45 of them had a history of previous minor stroke or transient ischemic attack ( TIA ) while 10 patients had cardiovascular risk factors but no previous cerebral ischemic event .  Endothelium-dependent changes in cerebral blood flow during the infusion of 30 g L-arginine were assessed by continuous transcranial Doppler sonography of both middle cerebral arteries , intima-media thickness ( IMT ) of the common carotid artery , by Duplex sonography . Associations between risk factors , IMT , L-arginine reactivity and previous cerebrovascular events were analyzed by stepwise multiple linear regression analysis and patient groups were compared . Results : Normal young volunteers showed an L-arginine-mediated increase in mean flow velocity of 22 ± 8 % ; L-arginine reactivity of the 55 patients was 28 ± 10 % . Patients with a history of stroke or TIA had significantly higher flow velocity responses to L-arginine ( 29 ± 10 % ) than patients with cardiovascular risk factors but no previous cerebrovascular event ( 21 ± 8 % , p < 0.05 ) . Stepwise multiple linear regression analysis showed a significant association of enhanced L-arginine reactivity with previous stroke/TIA ( p < 0.001 ) and elevated fibrinogen levels ( p < 0.05 ) but not with age , IMT , hypertension , cholesterol or other risk factors . The same regression model showed an association between IMT and previous stroke/TIA ( p < 0.001 ) and serum cholesterol levels ( p < 0.05 ) but not L-arginine reactivity . Conclusions : L-arginine reactivity of the cerebral vessels may be assessed by Doppler sonography and was enhanced in patients with a history of stroke or TIA . It was independent of IMT of the carotid arteries . We conclude that enhanced L-arginine reactivity is a potential marker for cerebral endothelial dysfunction and an independent indicator for an increased risk of stroke OBJECTIVE —Type 2 diabetes increases risk of stroke , perhaps because of impaired cerebrovascular basal nitric oxide ( NO ) activity . We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol . RESEARCH DESIGN AND METHODS —We performed a r and omized , double-blind , placebo-controlled crossover study . We measured the response to infusion of  NG-monomethyl-L-arginine ( l-NMMA ) in males with type 2 diabetes before and after allopurinol or placebo . The primary end point was the change in internal carotid artery flow following l-NMMA infusion , expressed as the area under the flow-per-time curve . RESULTS —We enrolled 14 participants .  Allopurinol improved responses to l-NMMA when compared with responses associated with placebo ( P = 0.032 ; median reduction in internal carotid artery flow following l-NMMA of 3,144 ml [ 95 % CI 375–7,143 ] ) . CONCLUSIONS —Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability , as evidence d by a 
    Output:
    
Endothelium-dependent vasodilatation ( EDV ) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis , but enhanced in CADASIL patients .
Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine .
Responses to l-NMMA deviated between subjects with type 2 DM and the elderly .