L-arginine plasma levels and severity of idiopathic pulmonary arterial hypertension

Beyer, Jan; Kolditz, Martin; Ewert, Ralf; Rubens, C.; Opitz, Christian; Schellong, Sebastian; Hoeffken, Gert; Halank, Michael

doi:10.1024/0301-1526.37.1.61

Cited by 16 publications

(7 citation statements)

References 22 publications

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“…The bioavailability of L-arginine to NOS has been shown to affect NO production [29]. For example, infants with persistent pulmonary hypertension of the newborn had lower plasma levels of L-arginine and lower plasma nitrates than did infants without pulmonary hypertension [2,25]. The mechanism of PH in the newborn, however, may be different than that of PH associated with congenital heart disease and this will also need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

et al. 2010

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Down syndrome (DS) patients have an increased risk of developing pulmonary hypertension (PH). Increased plasma levels of asymmetric dimethylarginine (ADMA) may contribute to vascular dysfunction in adults with idiopathic pulmonary hypertension. Our goal was to test the hypothesis that DS patients with PH have higher plasma levels of ADMA than DS patients without PH. DS patients with definitive PH (n = 6) and DS patients with no evidence of PH (n = 12) were studied. Plasma levels of arginine, ADMA, and nitrite/nitrate (NOx; stable metabolites of nitric oxide (NO)) were measured. Plasma arginine concentration was lower (p < 0.05) in PH patients (23 ± 11 μM) versus non-PH patients (46 ± 24 μM). Plasma ADMA concentration was higher (p < 0.005) in PH patients (18.0 ± 4.2 μM) versus non-PH patients (8.6 ± 5.9 μM). Plasma NOx was lower (p < 0.05) in PH patients (4.5 ± 1.7 μM) versus non-PH patients (8.5 ± 7.3 μM). These results are consistent with ADMA contributing to lower NO production in DS patients with PH and suggest that ADMA levels may be a potential biomarker for PH in DS patients.

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Section: Discussionmentioning

confidence: 99%

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

et al. 2010

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“…96 This leads to a depletion of L-arginine, which has been shown to be strongly correlated with right atrial pressure, cardiac index, and 6-min walk distance in patients with idiopathic PAH. 97 It is important to note that although increased arginase is associated with decreased NO production, arginase may also contribute to the vasculopathy of PAH through NO-independent pathways, especially via increased polyamine synthesis and the subsequent stimulation of vascular proliferation and remodelling. 14…”

Section: Pulmonary Arterial Hypertensionmentioning

confidence: 99%

Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal?

Pernow

Jung

2013

Cardiovascular Research

264

247

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Functional integrity of the vascular endothelium is of fundamental importance for normal vascular function. A key factor regulating endothelial function is the bioavailability of nitric oxide (NO). Recently, the enzyme arginase has emerged as an important regulator of NO production by competing for l-arginine, which is a substrate for both arginase and NO synthase. Increased activity of arginase may reduce the availability of l-arginine for NO synthase, thus reducing NO production, increasing formation of reactive oxygen species, and leading ultimately to endothelial dysfunction. Increased activity and expression of arginase have been demonstrated in several pathological cardiovascular conditions, including hypertension, pulmonary arterial hypertension, atherosclerosis, myocardial ischaemia, congestive heart failure, and vascular dysfunction in diabetes mellitus. Experimental studies have demonstrated that inhibition of arginase under these conditions increases NO bioavailability, reduces oxidative stress, improves vascular function, and protects against ischaemia-reperfusion injury. Initial clinical interventional studies are also promising. The purpose of this review is to discuss the role of arginase in cardiovascular pathologies, its contribution to the development of several cardiovascular disease states and the feasibility of using arginase inhibition as a therapeutic strategy.

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“…Still, in our study, there was a significant difference in l -arginine between PAH and LVSD and this is an important finding. Furthermore, Beyer et al showed a strong correlation between plasma l -arginine levels and severity of idiopathic PAH [ 32 ]. Currently, there are no known biomarkers to separate PAH to LVSD.…”

Section: Discussionmentioning

confidence: 99%

Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction

et al. 2017

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Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r s = −0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.

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L-arginine plasma levels and severity of idiopathic pulmonary arterial hypertension

Abstract: The results suggest a possible role of the NO precursor L-arginine in the pathogenesis of iPAH.

Cited by 16 publications

References 22 publications

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal?

Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction

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