Asymmetric dimethylarginine and asthma

Scott, Jeremy A.; Gauvreau, Gail M.; Grasemann, Hartmut

doi:10.1183/09031936.00080313

Cited by 13 publications

(14 citation statements)

References 7 publications

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“…Subjects with asthma have greater sputum ADMA levels when compared to healthy controls and a controlled allergen exposure results in an increase in sputum ADMA after 7 and 24 h [10,24]. Asthmatic children also have higher airway condensate ADMA levels when compared to healthy controls a difference not modified by use of inhaled corticosteroids [25].…”

Section: Discussionmentioning

confidence: 99%

l‐citrulline prevents asymmetric dimethylarginine‐mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells

Winnica

Que

Baffi

et al. 2016

Clin Experimental Allergy

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Introduction Asthma is associated with reduced systemic levels of L-arginine and increased asymmetric dimethylarginine (ADMA). This imbalance leads to nitric oxide synthase (NOS) uncoupling with reduced nitric oxide (NO) formation and greater oxidative and nitrosative stress. Whether this imbalance also occurs in the bronchial epithelium of asthmatics is unknown. Methods Subjects with asthma and healthy controls underwent bronchoscopy to obtain human bronchial epithelial cells (HBECs), which were cultured and stimulated with IL-13 and IFNγ (both 10ng/ml) to determine the effects of ADMA and varying concentrations of L-arginine, on NO- metabolites (nitrites + nitrates or NOx), hydrogen peroxide and nitrotyrosine levels. HBECs were also treated with L-citrulline to prevent ADMA-mediated effects in NO bioavailability and nitrosative stress. Results In HBECsIL-13 and IFNγ stimulated NOS2 and increased NOx levels. The addition of ADMA reduced NOx and increased H202 levels (p<0.001). Treatment with L-citrulline (800μM, 1600μM) rescued NOx when the L-arginine media concentration was 25 μM but failed to do so with higher concentrations (100μM). Under reduced L-arginine media conditions, HBECs treated with L-citrulline increased the levels of argininosuccinate, an enzyme that metabolizes L-citrulline to L-arginine. L-citrulline prevented the ADMA-mediated increase in nitrotyrosine in HBECs in cells from asthmatics and controls. Conclusion Increasing ADMA reduces NO formation and increases oxidative and nitrosative stress in airway epithelial cells. L-citrulline supplementation restores NO formation, while preventing nitrosative stress.

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Section: Discussionmentioning

confidence: 99%

l‐citrulline prevents asymmetric dimethylarginine‐mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells

Winnica

Que

Baffi

et al. 2016

Clin Experimental Allergy

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“…Chronic obstructive pulmonary disease (COPD) is characterized by obstruction of the airways and progressive airway restriction (22). The levels of ADMA could also increase in COPD patients (26). In our study, increased ADMA levels were observed in smoking and HT patients than in normal patients.…”

Section: Discussionmentioning

confidence: 46%

Association between Newly Diagnosed Essential Hypertension, Smoking, Assymetric Dimethylarginine and ischemia-Modified Albumin

Altuntaş¹,

Bengü²,

Kiraz³

et al. 2017

Istanbul Med J

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Essential hypertension (HT) is one of the major reasons for admission to hospitals worldwide; it is a preventable and curable disease. In case of long-term exposure, clinical pictures such as renal failure, heart failure, and blindness can occur (1).Because the endothelium is a vascular layer that has very important roles in the maintenance of normal vascular functions, its dysfunction leads to many diseases of the cardiovascular system. One of the important molecules that regulate endothelial functions is nitric oxide (NO). NO deficiency can cause endothelial dysfunction and many diseases, particularly cardiovascular disease (2). Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase (NOS) inhibitor. It inhibits local NO synthesis and causes endothelial dysfunction. It is considered as a risk factor for the development of coronary artery disease and essential HT (3).Ischemia-modified albumin (IMA) is a molecule that emerges due to a series of structural changes in the amino-terminal end binding metals in serum albumin (4). Its level increases due to oxidative stress, and one of the reasons for this increase is acute coronary syndrome (5).Smoking triggers many inflammatory disorders, particularly pulmonary diseases characterized by a progressive restriction in the airways. Although this process has not been clearly explained yet, it affects the extrapulmonary system (6).This study aimed to investigate the relationship between oxidative stress and increasing ADMA and IMA levels in patients with newly diagnosed HT and a history of smoking. MethodsThis study included 95 consecutive patients who presented to the outpatient clinic for any reason. The patients were divided into three groups: those who were healthy and non-smokers (Group 1, n=25), those who had left ventricular hypertrophy (LVH) accompanying newly diagnosed HT and were smokers (Group 2, n=35), and those who had LVH accompanying newly diagnosed HT Association between Newly Diagnosed Essential Hypertension, Smoking, Assymetric Dimethylarginine and ischemia-Modified AlbuminObjective: This study aimed to investigate the relationship between increasing levels of assymetric dimethylarginine (ADMA)and ischemia-modified albumin (IMA) in people with early diagnosis of hypertension (HT) and smoking history. Methods:The study included 95 outpatients who visited our hospital. Patients were classified into three groups: group 1, healthy and non-smokers (n=25); group 2, no smoker patients with newly diagnosed essential HT with LVH (left ventricle hypertrophia) (n=35); group 3, smoking patients with a LVH accompanying newly diagnosed essential HT (n=35). 51% of patients are females; 49% of them are males.The trial was approved by the local ethics committee. Blood samples were analyzed, which were taken after 8 h of fasting. Biochemical parameters such as, C reactive protein (CRP), ADMA, IMA values were recorded. Using echocardiography, cardiac values were recorded. Results:In this study, the first group consisted of 25 patients and second and third group of ...

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“…In contrast, in adults with severe asthma, ADMA levels were higher than those observed in subjects with mild to moderate asthma . Given the interference of ADMA with NO production and previous findings of an increase in airway ADMA levels after allergen challenge , the measurement of ADMA in our experimental setting was reasonable for a sound interpretation of NO dynamics during SIC. The lack of differences in ADMA concentrations between SIC+ and SIC− groups suggests that ADMA has no relevant role on the changes in NO production induced by diisocyanate.…”

Section: Discussionmentioning

confidence: 46%

“…The formation of asymmetric dimethyl arginine (ADMA), a product of methylation of l ‐arginine, could modulate NO production in the lung through its ability to inhibit NOS isoforms . Because a significant increase in sputum ADMA was demonstrated after allergen challenge in subjects with allergic asthma, NO detected in exhaled air in this condition results from a balance between up‐regulation of inducible NOS by allergic inflammation and NOSs inhibition by ADMA . Whether the changes in ADMA occur upon SIC with isocyanates is unknown.…”

Section: Introductionmentioning

confidence: 99%