Physical training and metabolics of nitric oxide in individuals with idiopathic pulmonary arterial hypertension

2019 ◽  
Author(s):  
Aline Marsico ◽  
Etiene Teixeira De Carvalho ◽  
Vivian Arakelian ◽  
Flávia Navarro ◽  
Fernanda Consolim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Physical Training ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals Correction to: Exhaled nitric oxide is not a biomarker for idiopathic pulmonary arterial hypertension or for treatment efficacy

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Majid Malekmohammad ◽  
Gert Folkerts ◽  
Babak Sharif Kashani ◽  
Parisa Adimi Naghan ◽  
Zahra Habibi Dastenae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Treatment Efficacy ◽  
Exhaled Nitric Oxide ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial

Following publication of the original article [1], the authors flagged that name of the author ‘Batoul Khoundabi’ had been provided with an incorrect spelling: ‘Batoutl’ was given in place of ‘Batoul’.

scholarly journals Exhaled nitric oxide is not a biomarker for idiopathic pulmonary arterial hypertension or for treatment efficacy

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Majid Malekmohammad ◽  
Gert Folkerts ◽  
Babak Sharif Kashani ◽  
Parisa Adimi Naghan ◽  
Zahra Habibi Dastenae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Disease Severity ◽  
Exhaled Nitric Oxide ◽  
Functional Class ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Control Group ◽  
Significant Difference ◽  
Pulmonary Arterial

Abstract Background Idiopathic pulmonary arterial hypertension (IPAH) is a fatal illness. Despite many improvements in the treatment of these patients, there is no unique prognostic variable available to track these patients. The aim of this study was to evaluate the association between fractional exhaled nitric oxide (FeNO) levels, as a noninvasive biomarker, with disease severity and treatment outcome. Methods Thirty-six patients (29 women and 7 men, mean age 38.4 ± 11.3 years) with IPAH referred to the outpatient’s clinic of Masih Daneshvari Hospital, Tehran, Iran, were enrolled into this pilot observational study. Echocardiography, six-minute walking test (6MWT), FeNO, brain natriuretic peptide (BNP) levels and the functional class of patients was assessed before patients started treatment. Assessments were repeated after three months. 30 healthy non-IPAH subjects were recruited as control subjects. Results There was no significant difference in FeNO levels at baseline between patients with IPAH and subjects in the control group. There was also no significant increase in FeNO levels during the three months of treatment and levels did not correlate with other disease measures. In contrast, other markers of disease severity were correlated with treatment effect over the three months. Conclusion FeNO levels are a poor non-invasive measure of IPAH severity and of treatment response in patients in this pilot study.

Disease-specific platelet signaling defects in idiopathic pulmonary arterial hypertension

2021 ◽  
Vol 320 (5) ◽  
pp. L739-L749
Author(s):  
Kulwant S. Aulak ◽  
Sami Al Abdi ◽  
Ling Li ◽  
Jack S. Crabb ◽  
Arnab Ghosh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Specific Activity ◽  
Ex Vivo ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Therapeutic Decisions ◽  
Pulmonary Arterial ◽  
Disease Specific

Idiopathic pulmonary arterial hypertension (IPAH) is a rapidly progressive disease with several treatment options. Long-term mortality remains high with great heterogeneity in treatment response. Even though most of the pathology of IPAH is observed in the lung, there is systemic involvement. Platelets from patients with IPAH have characteristic metabolic shifts and defects in activation; therefore, we investigated whether they could be used to identify other disease-specific abnormalities. We used proteomics to investigate protein expression changes in platelets from patients with IPAH compared with healthy controls. Key abnormalities of nitric oxide pathway were tested in platelets from a larger cohort of unique patients with IPAH. Platelets showed abnormalities in the prostacyclin and nitric oxide pathways, which are dysregulated in IPAH and hence targets of therapy. We detected reduced expression of G protein αs and increased expression of the regulatory subunits of the cAMP-dependent protein kinase (PKA) type II isoforms, supporting an overall decrease in the activation of the prostacyclin pathway. We noted reduced levels of the soluble guanylate cyclase (sGC) subunits and increased expression of the phosphodiesterase type 5 A (PDE5A), conditions that affect the response to nitric oxide. Ensuing analysis of 38 unique patients with IPAH demonstrated considerable variation in the levels and specific activity of sGC, a finding with novel implications for personalized therapy. Platelets have some of the characteristic vasoactive signal abnormalities seen in IPAH and may provide comprehensive ex vivo mechanistic information to direct therapeutic decisions.

scholarly journals Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension

2016 ◽  
Vol 48 (5) ◽  
pp. 1386-1395 ◽  
Author(s):  
Rui Zhang ◽  
Xiao-Jian Wang ◽  
Hong-Da Zhang ◽  
Xiao-Qing Sun ◽  
Qin-Hua Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Prognostic Indicator ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Plasma Metabolites ◽  
Mean Pulmonary Arterial Pressure ◽  
Increased Risk ◽  
Pulmonary Arterial ◽  
The Impact

Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (μmol·L−1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of ≤10 μmol·L−1 had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH.

scholarly journals Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: role of nitric oxide

2012 ◽  
Vol 302 (6) ◽  
pp. L512-L520 ◽  
Author(s):  
Metin Aytekin ◽  
Kulwant S. Aulak ◽  
Sarah Haserodt ◽  
Ritu Chakravarti ◽  
Joseph Cody ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Platelet Function ◽  
Cellular Proliferation ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Original Research ◽  
No Production ◽  
Pulmonary Arterial

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease. Several processes are believed to lead to the fatal progressive pulmonary arterial narrowing seen in IPAH including vasoconstriction, cellular proliferation inflammation, vascular remodeling, abnormalities in the lung matrix, and in situ thrombosis. Nitric oxide (NO) produced by NO synthases (NOS) is a potent vasodilator and plays important roles in many other processes including platelet function. Reduced NO levels in patients with IPAH are known to contribute to the development of pulmonary hypertension and its complications. Platelet defects have been implied in IPAH, but original research supporting this hypothesis has been limited. Normal platelets are known to have NOS activity, but little is known about NOS expression and NO production by platelets in patients with IPAH. Here we characterized the phenotype of the platelets in IPAH and show a defect in their ability to be activated in vitro by thrombin receptor activating protein but not adenosine diphosphate. We also show that endothelial NOS (eNOS) levels in these platelets are reduced and demonstrate that NO is an important regulator of platelet function. Thus reduced levels of eNOS in platelets could impact their ability to regulate their own function appropriately.

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