scholarly journals Impaired nitric oxide bioavailability and l-arginine–reversible endothelial dysfunction in adults with falciparum malaria

2007 ◽  
Vol 204 (11) ◽  
pp. 2693-2704 ◽  
Author(s):  
Tsin W. Yeo ◽  
Daniel A. Lampah ◽  
Retno Gitawati ◽  
Emiliana Tjitra ◽  
Enny Kenangalem ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Falciparum Malaria ◽  
Reactive Hyperemia ◽  
Severe Disease ◽  
Microvascular Endothelium ◽  
Tissue Ischemia ◽  
Exhaled No ◽  
No Bioavailability ◽  
Severe Falciparum Malaria

Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in SM but can be improved by l-arginine in cardiovascular disease. In an observational study in Indonesia, we measured endothelial function using reactive hyperemia–peripheral arterial tonometry (RH-PAT) in 51 adults with SM, 48 patients with moderately severe falciparum malaria (MSM), and 48 controls. The mean RH-PAT index was lower in SM (1.41; 95% confidence interval [CI] = 1.33–1.47) than in MSM (1.82; 95% CI = 1.7–2.02) and controls (1.93; 95% CI = 1.8–2.06; P < 0.0001). Endothelial dysfunction was associated with elevated blood lactate and measures of hemolysis. Exhaled NO was also lower in SM relative to MSM and controls. In an ascending dose study of intravenous l-arginine in 30 more patients with MSM, l-arginine increased the RH-PAT index by 19% (95% CI = 6–34; P = 0.006) and exhaled NO by 55% (95% CI = 32–73; P < 0.0001) without important side effects. Hypoargininemia and hemolysis likely reduce NO bioavailability. Endothelial dysfunction in malaria is nearly universal in severe disease, is reversible with l-arginine, and likely contributes to its pathogenesis. Clinical trials in SM of adjunctive agents to improve endothelial NO bioavailability, including l-arginine, are warranted.

scholarly journals Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

2015 ◽  
Vol 60 (1) ◽  
pp. 198-205 ◽  
Author(s):  
Janneke M. Brussee ◽  
Tsin W. Yeo ◽  
Daniel A. Lampah ◽  
Nicholas M. Anstey ◽  
Stephen B. Duffull
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Therapeutic Range ◽  
Time Course ◽  
Pkpd Model ◽  
Exhaled No ◽  
Optimal Dosing ◽  
Severe Falciparum Malaria

ABSTRACTImpaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations ofl-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctivel-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g ofl-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens forl-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen forl-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions ofl-arginine on NO and microvascular reactivity in severe malaria.

CD14+CD16++ “nonclassical” monocytes are associated with endothelial dysfunction in patients with coronary artery disease

2017 ◽  
Vol 117 (05) ◽  
pp. 971-980 ◽  
Author(s):  
Karol Urbanski ◽  
Dominik Ludew ◽  
Grzegorz Filip ◽  
Magdalena Filip ◽  
Agnieszka Sagan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mononuclear Cells ◽  
Vascular Dysfunction ◽  
Activation Markers ◽  
Mammary Arteries ◽  
No Bioavailability ◽  
Artery Disease

SummaryEndothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16– “classical – Mon1”, CD14++CD16+ “intermediate – Mon2” and CD14+CD16++ “nonclassical – Mon3”), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium- nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ “nonclassical” and low CD14++CD16- “classical” monocytes presented impaired endothelial function. High frequency of CD14+CD16++ “nonclassical” monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β =0.18 p=0.04 and β =-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ “nonclassical” monocytes are associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular reactive oxygen species production.

Abstract 1421: In Vivo Measurement of Flow-Mediated Vasodilation in Living Rats using High Resolution Ultrasound: Age-Dependent Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christian Heiss ◽  
Richard E Sievers ◽  
Nicolas Amabile ◽  
Tony Y Momma ◽  
Shobha Natarajan ◽  
...  
Keyword(s):  
High Resolution ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Reactive Hyperemia ◽  
Surrogate Marker ◽  
Flow Measurements ◽  
Age Related ◽  
Age Dependent

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.

scholarly journals The Relationship Between the Impairment of Endothelial Function and Thyroid Antibodies in Hashimoto’s Thyroiditis Patients with Euthyroidism

2020 ◽  
Vol 52 (09) ◽  
pp. 642-646
Author(s):  
Yanjin Hu ◽  
Zhi Yao ◽  
Guang Wang
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Hashimoto’S Thyroiditis ◽  
Reactive Hyperemia ◽  
Density Lipoprotein ◽  
Hashimoto Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Healthy Controls ◽  
Negatively Associated

AbstractEndothelial dysfunction is the important early step in the development of atherosclerosis. Hypothyroidism caused by Hashimoto’s thyroiditis and other thyroid disease is one of the risk factors of endothelial dysfunction. The present study tried to investigate the endothelial function and its associated factors in Hashimoto thyroiditis with euthyroidism. A total of 95 newly diagnosed Hashimoto’s thyroiditis patients with euthyroidism and 45 healthy controls were studied. Hashimoto’s patients were divided into 3 subgroups namely, single thyroglobulin antibody (TGAb) positive subgroup, single thyroid peroxidase antibody (TPOAb) positive subgroup, and both TGAb and TPOAb positive subgroup. Endothelial function was tested by the reactive hyperemia index (RHI). Hashimoto’s thyroiditis patients had lower RHI than healthy controls (1.73±0.42 vs 1.96±0.51, p<0.05). Hashimoto’s thyroiditis with single TGAb positive patients had higher RHI than single TPOAb positive (1.98±0.57 vs. 1.69±0.33, p<0.05) and TGAB + TPOAb positive patients (1.98±0.57 vs. 1.68±0.42, p<0.05). RHI were negatively associated with total cholesterol (TC, r=−0.215, p<0.05), low density lipoprotein cholesterol (LDL-C, r=−0.268, p<0.05), triglyceride (TG, r=−0.192, p<0.05), and TPOAb (r=−0.288, p<0.05). In the regression analysis, LDL-C (β=−0.146, p<0.05), TG (β=−0.034, p<0.05) and TPOAb (β=−0.001, p<0.05) were independently associated with RHI. Hashimoto’s patients had poor endothelial function. TPOAb levels were negatively associated with endothelial function.

scholarly journals Asymmetric Dimethylarginine in Adult Falciparum Malaria: Relationships With Disease Severity, Antimalarial Treatment, Hemolysis, and Inflammation

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Bridget E. Barber ◽  
Timothy William ◽  
Matthew J. Grigg ◽  
Uma Parameswaran ◽  
Kim A. Piera ◽  
...  
Keyword(s):  
Falciparum Malaria ◽  
Asymmetric Dimethylarginine ◽  
Interleukin 10 ◽  
Antimalarial Treatment ◽  
Factors Associated ◽  
Plasma Adma ◽  
No Bioavailability ◽  
Baseline Levels ◽  
Endothelial Nitric Oxide ◽  
Severe Falciparum Malaria

Abstract Background.  Endothelial nitric oxide (NO) bioavailability is impaired in severe falciparum malaria (SM). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (NOS), contributes to endothelial dysfunction and is associated with mortality in adults with falciparum malaria. However, factors associated with ADMA in malaria, including the NOS-substrate l-arginine, hemolysis, and antimalarial treatment, are not well understood. Methods.  In a prospective observational study of Malaysian adults with SM (N = 22) and non-SM (NSM; N = 124) and healthy controls (HCs), we investigated factors associated with plasma ADMA including the effects of antimalarial treatment. Results.  Compared with HCs, ADMA levels were lower in NSM (0.488 µM vs 0.540 µM, P = .001) and in the subset of SM patients enrolled before commencing treatment (0.453 µM [N = 5], P = .068), but levels were higher in SM patients enrolled after commencing antimalarial treatment (0.610 µM [N = 17], P = .026). In SM and NSM, ADMA levels increased significantly to above-baseline levels by day 3. Baseline ADMA was correlated with arginine and cell-free hemoglobin in SM and NSM and inversely correlated with interleukin-10 in NSM. Arginine and the arginine/ADMA ratio (reflective of arginine bioavailability) were lower in SM and NSM compared with HCs, and the arginine/ADMA ratio was lower in SM compared with NSM. Conclusions.  Pretreatment ADMA concentrations and l-arginine bioavailability are reduced in SM and NSM. Asymmetric dimethylarginine increases to above-baseline levels after commencement of antimalarial treatment. Arginine, hemolysis, and posttreatment inflammation all likely contribute to ADMA regulation, with ADMA likely contributing to the reduced NO bioavailability in SM.

The role of insulin and the adipocytokines in regulation of vascular endothelial function

2004 ◽  
Vol 107 (6) ◽  
pp. 519-532 ◽  
Author(s):  
Stuart A. RITCHIE ◽  
Marie-Ann EWART ◽  
Colin G. PERRY ◽  
John M. C. CONNELL ◽  
Ian P. SALT
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Insulin Signalling ◽  
Direct Effects ◽  
Paracrine Factors ◽  
Vascular Integrity ◽  
Beneficial Effects ◽  
Glucose Homoeostasis ◽  
No Bioavailability

Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability. Therefore altered insulin signalling in the endothelium represents a candidate mechanism underlying the association between insulin resistance and endothelial dysfunction. In recent years, it has become apparent that insulin sensitivity is regulated by the adipocytokines, a group of bioactive proteins secreted by adipose tissue. Secretion of adipocytokines is altered in obese individuals and there is increasing evidence that the adipocytokines have direct effects on the vascular endothelium. A number of current antidiabetic strategies have been demonstrated to have beneficial effects on endothelial function and to alter adipocytokine concentrations in addition to their effects on glucose homoeostasis. In this review we will explore the notion that the association between insulin resistance and endothelial dysfunction is accounted for by adipocytokine action on the endothelium. In addition, we examine the effects of weight loss, exercise and antidiabetic drugs on adipocytokine availability and endothelial function.

scholarly journals Antioxidant Treatment Reverts Increased Arterial Basal Tone and Oxidative Stress in Nephrectomized (5/6) Hypertensive Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Rodrigo O. Marañón ◽  
Claudio Joo Turoni ◽  
Maria Sofia Karbiner ◽  
Nicolas Salas ◽  
Maria Peral de Bruno
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Basal Tone ◽  
No Bioavailability

Nonischemic 5/6 nephrectomized rat (NefR) is a model of chronic kidney disease. However, little is known about vascular dysfunction and its relation with hypertension in NefR.Aims. To evaluate possible alterations of endothelial function, NO-bioavailability, and basal tone in aorta from NefR and the role of oxidative stress. Sprague Dawley rats were divided into sham rats (SR), NefR, and NefR treated with tempol (NefR-T). Mean arterial pressure (MAP) and renal function were determined. In isolated aortic rings the following was measured: 1-endothelial function, 2-basal tone, 3-NO levels, 4-membrane potential (MP), and 5-oxidative stress. NefR increased MAP (SR: 119 ± 4 mmHg;n=7; NefR: 169 ± 6;n=8;P<0.001). Tempol did not modify MAP (NefR-T: 168 ± 10;n=6;P<0.001). NefR showed endothelial dysfunction, increased basal tone and decreased NO levels (SR: 32 ± 2 nA;n=7, NefR: 10 ± 2;n=8;P<0.001). In both in vitro and in vivo tempol improves basal tone, NO levels, and MP. Oxidative stress in NefR was reverted in NefR-T. We described, for the first time, that aorta from NefR presented increased basal tone related to endothelial dysfunction and decreased NO-bioavailability. The fact that tempol improves NO-contents and basal tone, without decrease MAP, indicates that oxidative stress could be implicated early and independently to hypertension, in the vascular alterations.

scholarly journals Arterial elasticity, endothelial function and intracranial vascular health: A multimodal MRI study

2020 ◽  
pp. 0271678X2095695
Author(s):  
Wenjin Liu ◽  
Zhensen Chen ◽  
Dakota Ortega ◽  
Xuebing Liu ◽  
Xiaoqin Huang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Reactive Hyperemia ◽  
Brain Perfusion ◽  
Cerebrovascular Diseases ◽  
White Matter Hyperintensity ◽  
Arterial Elasticity ◽  
Vascular Health

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries.

scholarly journals STUDY OF VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
pp. 81-89
Author(s):  
Maryna Stoikevych ◽  
Nataliia Nedzvetska ◽  
Nataliia Fedorova
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Endothelium ◽  
Bowel Disease ◽  
Reactive Hyperemia ◽  
Vascular Endothelial ◽  
Inflammatory Bowel

Abstract. Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p < 0.001) and 2.6 times more often than PFE (c2 = 31.5; p < 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p < 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p < 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p < 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p < 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.

scholarly journals Nitric Oxide–Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease

2016 ◽  
Vol 214 (10) ◽  
pp. 1557-1564 ◽  
Author(s):  
Bridget E. Barber ◽  
Timothy William ◽  
Matthew J. Grigg ◽  
Kim A. Piera ◽  
Youwei Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Severe Disease ◽  
Healthy Controls ◽  
Intravascular Hemolysis ◽  
Plasmodium Vivax Malaria ◽  
Arginine Level

Background Pathogenesis of severe Plasmodium vivax malaria is poorly understood. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability characterize severe falciparum malaria, but have not been assessed in severe vivax malaria. Methods In patients with severe vivax malaria (n = 9), patients with nonsevere vivax malaria (n = 58), and healthy controls (n = 79), we measured NO-dependent endothelial function by using reactive hyperemia–peripheral arterial tonometry (RH-PAT) and assessed associations with arginine, asymmetric dimethylarginine (ADMA), and hemolysis. Results The L-arginine level and the L-arginine to ADMA ratio (a measure of L-arginine bioavailability) were reduced in patients with severe vivax malaria and those with nonsevere vivax malaria, compared with healthy controls (median L-arginine level, 65, 66, and 98 µmol/mL, respectively [P = .0001]; median L-arginine to ADMA ratio, 115, 125, and 187, respectively [P = .0001]). Endothelial function was impaired in proportion to disease severity (median RH-PAT index, 1.49, 1.73, and 1.97 in patients with severe vivax malaria, those with nonsevere vivax malaria, and healthy controls, respectively; P = .018) and was associated with the L-arginine to ADMA ratio. While the posttreatment fall in hemoglobin level was greater in severe vivax malaria as compared to nonsevere vivax malaria (2.5 vs 1 g/dL; P = .0001), markers of intravascular hemolysis were not higher in severe disease. Conclusions Endothelial function is impaired in nonsevere and severe vivax malaria, is associated with reduced L-arginine bioavailability, and may contribute to microvascular pathogenesis. Severe disease appears to be more associated with extravascular hemolysis than with intravascular hemolysis.

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