***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: The mechanisms underlying the  skin blood flow ( SkBF ) response  to local heating are complex and poorly understood . Our goal was to examine the role of axon reflexes and nitric oxide ( NO ) in the SkBF response to a local heating protocol . We performed 40 experiments following a st and ardized heating protocol  with different interventions , including blockade of the axon reflex ( EMLA cream ) , antebrachial nerve blockade ( 0.5 % bupivacaine injection ) , and NO synthase ( NOS ) inhibition ( > or = 10 mM N(G)-nitro-L-arginine methyl ester ; microdialysis ) . Appropriate controls were performed to verify the efficacy of the various blocks . Values are expressed as a percentage of maximal SkBF ( SkBF(max ) ; 50 mM sodium nitroprusside ) . At the initiation of local heating , SkBF rose to an initial peak , followed by a brief nadir , and a secondary , progressive rise to a plateau . Axon reflex block decreased the initial peak from 75 + 3 to 32 + /- 2 % SkBF(max ) ( P < 0.01 vs. control ) but did not affect the plateau . NOS inhibition before and throughout local heating reduced the initial peak from 75 + /- 3 to 56 + /- 3 % SkBF(max ) ( P < 0.01 ) and the plateau from 87 + /- 4 to 40 + /- 5 % . NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone . Antebrachial nerve block did not affect the local heating SkBF response . The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating : a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients .  Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity Regular physical activity leads to increased endothelium-dependent vasodilatation . Postocclusive reactive hyperemia ( PRH ) is a transient increase of blood flow after the release of an arterial occlusion and has been used as a clinical tool to estimate endothelial function . The aim of our study was to assess the potential effect of regular physical training on PRH of skin microcirculation . Skin blood flux was estimated by laser-Doppler fluxmetry ( LDF ) in two groups of subjects : 12 highly trained athletes and 12 age-matched sedentary controls .  LDF was measured on two specific skin sites : volar aspect of the forearm ( nonglabrous area ) and finger pulp of the middle finger ( glabrous area ) . After the release of a 3-min occlusion of the brachial artery , we determined the following indices of PRH : the time to peak ( tpeak ) , the maximal LDF ( LDFpeak ) , the recovery time ( trec ) , the area under the PRH curve ( AUC ) . Baseline LDF did not differ between the trained and sedentary subjects in either site . On the forearm , we found no significant differences in either PRH parameter . On the contrary , on the finger pulp , there were statistically significant differences in the tpeak and the AUC ( p < or = 0.05 ) . The results show an altered PRH response of skin microcirculation in the finger pulp in the trained subjects . We may speculate that this could be the result of an increased endothelial vasodilator capacity . Further , the potential adaptations of the endothelium differ between the glabrous and nonglabrous skin sites BACKGROUND Aging is associated with increased cardiovascular risk and endothelial dysfunction . Since exercise can improve endothelium-dependent vasodilation , in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction . METHODS AND RESULTS In 12 young and elderly ( age 26.9+/-2.3 and 62.9+/-5.8 years , respectively ) healthy sedentary subjects and 11 young and 14 elderly matched athletes ( age 27.5+/-1.9 and 66.4+/-6.1 years , respectively ) , we studied ( with strain-gauge plethysmography ) forearm blood flow modifications induced by intrabrachial acetylcholine ( 0.15 , 0.45 , 1.5 , 4.5 , and 15 microg/100 mL per minute ) , an endothelium-dependent vasodilator , at baseline , during infusion of N(G)-monomethyl-L-arginine ( L-NMMA ) ( 100 microg/100 mL forearm tissue per minute ) , a nitric oxide-synthase inhibitor , vitamin C ( 8 mg/100 mL forearm tissue per minute ) , an antioxidant , and finally under simultaneous infusion of L-NMMA and vitamin C. The response to  sodium nitroprusside ( 1 , 2 , and 4 microg/100 mL forearm tissue per minute ) was also evaluated . In young athletes and sedentary subgroups , vasodilation to acetylcholine was inhibited by L-NMMA and was not changed by vitamin C. In elderly subjects , vasodilation to acetylcholine was blunted as compared with young subjects in both control subjects and athletes , whereas the response to sodium nitroprusside was similar . Moreover , in elderly athletes , vitamin C did not change the vasodilation to acetylcholine . In contrast , in elderly sedentary subjects , the response to acetylcholine was resistant to L-NMMA . In this subgroup , vitamin C increased the vasodilation to acetylcholine and restored the inhibiting effect of L-NMMA . CONCLUSIONS These results suggest that regular physical activity can at least in part prevent the age-induced endothelial dysfunction , probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress For centuries , the general consensus has been that vigorous , competitive exercise was harmful and shortened life expectancy . Recent data from prospect i ve cohort studies conducted on marathon runners , professional cyclists , and Olympic athletes indicate , however , that regular intense endurance-exercise training has protective benefits against cardiovascular disease and premature death . There are still important questions to be answered , such as what is the optimal dose , in terms of both duration and intensity of training or competition , beyond which the health benefits of regular exercise stabilize or might even potentially disappear Background — Higher levels of physical activity are associated with fewer cardiovascular disease  (  CVD ) events . Although the precise mechanisms underlying this inverse association are unclear , differences in several cardiovascular risk factors may mediate this effect . Methods and Results — In a prospect i ve study of 27 055 apparently healthy women , we measured baseline levels of hemoglobin A1c , traditional lipids ( total , low-density lipoprotein , and high-density lipoprotein cholesterol ) , novel lipids [ lipoprotein(a ) and apolipoprotein A1 and B-100 ] , creatinine , homocysteine , and inflammatory/hemostatic biomarkers  ( high-sensitivity C-reactive protein , fibrinogen , soluble intracellular adhesion molecule-1 ) and used women 's self-reported physical activity , weight , height , hypertension , and diabetes . Mean follow-up was 10.9±1.6 years , and 979 incident CVD events occurred . The risk of CVD decreased linearly with higher levels of activity ( P for linear trend < 0.001 ) . Using the reference group of < 200 kcal/wk of activity yielded age- and treatment-adjusted relative risk reductions associated with 200 to 599 , 600 to 1499 , and ≥1500 kcal/wk of 27 % , 32 % , and 41 % , respectively . Differences in known risk factors explained a large proportion ( 59.0 % ) of the observed inverse association . When sets of risk factors were examined , inflammatory/hemostatic biomarkers made the largest contribution to lower risk ( 32.6 % ) , followed by blood pressure ( 27.1 % ) . Novel lipids contributed less to CVD risk reduction compared with traditional lipids ( 15.5 % and 19.1 % , respectively ) . Smaller contributions were attributed to body mass index ( 10.1 % ) and hemoglobin A1c/diabetes ( 8.9 % ) , whereas homocysteine and creatinine had negligible effects ( < 1 % ) . Conclusions — The inverse association between  physical activity  and CVD risk is mediated in substantial part by known risk factors , particularly inflammatory/hemostatic factors and blood pressure BACKGROUND The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure ( CHF ) . Endothelial dysfunction is a key feature of CHF , contributing to increased peripheral vasoconstriction and impaired exercise capacity . Local h and grip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF . METHODS AND RESULTS Twenty patients were prospect ively r and omized to a training group ( n=10 , left ventricular ejection fraction [ LVEF ] 24+/-4 % ) or a control group ( n=10 , LVEF 23+/-3 % ) . At baseline and after 6 months , peak flow velocity was measured in the left femoral artery using a Doppler wire ; vessel diameter was determined by quantitative angiography . Peripheral blood flow was calculated from average peak velocity ( APV ) and arterial cross-sectional area . After exercise training , nitroglycerin-induced endothelium-independent vasodilation remained unaltered ( 271 % versus 281 % , P = NS ) . Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203 % ( from 152+/-79 to 461+/-104 mL/min , P<0.05 versus control group ) and the inhibiting effect of L-NMMA increased by 174 % ( from -46+/-25 to -126+/-19 mL/min , P<0.05 versus control group ) . Peak oxygen uptake increased by 26 % ( P<0.01 versus control group ) . The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow ( r=0.64 , P<0 . 005 ) . CONCLUSIONS Regular physical exercise improves both basal endothelial nitric oxide ( NO ) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF . The correction of endothelium dysfunction is associated with a significant increase in exercise capacity BACKGROUND The health benefits of leisure-time physical activity are well known , but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear . We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population . METHODS In this prospect i ve cohort study , 416,175 individuals ( 199,265 men and 216,910 women ) participated in a st and ard medical screening programme in Taiwan between 1996 and 2008 , with an average follow-up of 8·05 years ( SD 4·21 ) . On the basis of the amount of weekly exercise indicated in a self-administered question naire , participants were placed into one of five categories of exercise volumes : inactive , or low , medium , high , or very high activity . We calculated hazard ratios ( H 
    Output:
    
Both young and master athletes present enhanced microvascular function compared with age-matched untrained but otherwise healthy subjects .
These data provide evidence of a positive association between  exercise training  and microvascular function in the absence of known underlying cardiovascular disease