Exhaled nitric oxide and pulmonary response to iloprost in systemic sclerosis with pulmonary hypertension

Rolla, Giovanni; Colagrande, Paola; Brussino, Luisa; Bucca, Caterina; Bertero, Maria Tiziana; Caligaris-Cappio, Federico

doi:10.1016/s0140-6736(05)78874-7

Cited by 25 publications

(16 citation statements)

References 4 publications

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“…Capillary microscopic findings and proximal nailfold biopsy specimens have been studied .48 The severity of periodic acid‐Schiff‐positive serous cuticular deposits correlated with the severity of the capillary microscopic pattern. A generalized microvascular endothelial dysfunction has been found even in the uninvolved skin of SSc .49 Substance P‐mediated pulmonary vasodilation is absent in SSc, suggesting that endothelial dysfunction occurs early in the course of the illness .50 These findings confirm that vascular disturbance has been detected in clinical practice as well as nailfold capillary microscopic studies. The existence of antiendothelial antibodies has been reported in SSc.…”

Section: The Importance Of Vascular Disturbances In Patients With Syssupporting

confidence: 67%

Quantitative analysis of nailfold capillary abnormalities in patients with connective tissue diseases

Ohtsuka

1999

Int J Dermatology

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Section: The Importance Of Vascular Disturbances In Patients With Syssupporting

confidence: 67%

Quantitative analysis of nailfold capillary abnormalities in patients with connective tissue diseases

Ohtsuka

1999

Int J Dermatology

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“…In previous studies, the efficacy of iloprost has been evaluated in acute vasodilator testing, 13 and the experience with long-term treatment of three patients has been reported. [13][14][15] Based on these data, we attempted a switch from long-term IV epoprostenol to inhaled iloprost in three patients with severe pulmonary hypertension.…”

Section: (Chest 2001; 119:296 -300)mentioning

confidence: 99%

Aerosolized Iloprost Therapy Could Not Replace Long-term IV Epoprostenol (Prostacyclin) Administration in Severe Pulmonary Hypertension

Schenk¹,

Petkov²,

Madl³

et al. 2001

Chest

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“…In systemic sclerosis (SSc) patients, NO is increased in exhaled air [1,2] while it is decreased in those patients with pulmonary hypertension [2,3]. Moreover, serum NO levels are enhanced [4], iNOS is highly expressed in mononuclear cells infiltrating the skin [4] and peripheral blood mononuclear cells produce increased NO levels when stimulated with IL-1 [5].…”

mentioning

confidence: 99%

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

et al. 2002

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Lung macrophages may play a relevant role in oxidative processes producing both superoxide anion ðO À 2 Þ and NO. In this view, an antioxidant therapy can be useful in the treatment of systemic sclerosis (SSc) patients. N-Acetylcysteine (NAC) is able to expand natural antioxidant defenses by increasing intracellular gluthatione concentration and it has been proposed as an antioxidant therapy in respiratory distress syndromes. The aim of our study was to determine whether lung macrophages obtained from SSc patient bronchoalveolar lavage (BAL) express the inducible form of nitric oxide synthase (iNOS) and whether NAC can reduce the peroxynitrite ðONOO À Þ and O À 2 production of these cells. Alveolar macrophages were isolated from BAL of 32 patients and used for the immunocytochemical determination of iNOS, and the production of ONOO À and O À 2 was measured by fluorimetric or spectrophotometric methods, respectively. Lung macrophages obtained from SSc patients expressed a higher level of iNOS compared to healthy subject cells. NAC preincubation (5 Â 10 À5 M, 24 h) significantly reduced ()21%) the ONOO À production in formyl Met-Leu-Phe (fMLP)-activated cells and slightly reduced it under resting conditions, whereas NAC preincubation was unable to modify the release of O À 2 both in basal condition and in fMLP-stimulated cells. We conclude that since SSc lung macrophages express high levels of iNOS and produce a significant quantity of ONOO À , NAC administration reduces ONOO À production and can be an useful treatment to alleviate SSc symptoms. Ó 2002 Elsevier Science (USA). All rights reserved.Keywords: Systemic sclerosis; Inducible nitric oxide synthase; N-acetylcysteine; Peroxynitrite; Superoxide anion; Alveolar macrophages Nitric oxide (NO) 1 is physiologically produced by constitutive nitric oxide synthase isoforms (cNOS) and in several pathophysiological conditions by an inducible nitric oxide synthase isoform (iNOS). In systemic sclerosis (SSc) patients, NO is increased in exhaled air [1,2] while it is decreased in those patients with pulmonary hypertension [2,3]. Moreover, serum NO levels are enhanced [4], iNOS is highly expressed in mononuclear cells infiltrating the skin [4] and peripheral blood mononuclear cells produce increased NO levels when stimulated with IL-1 [5]. NO can be synthesized by different kinds of cells. Among these cells, macrophages play a pivotal role in the inflammatory infiltrate and, in patients with tubercolosis, iNOS is expressed in alveolar macrophages [6]. Inflammatory cells produce reactive oxygen species (ROS) that, reacting with NO, form tissue-damaging NO-derived inflammatory oxidants. ROS

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Exhaled nitric oxide and pulmonary response to iloprost in systemic sclerosis with pulmonary hypertension

Cited by 25 publications

References 4 publications

Quantitative analysis of nailfold capillary abnormalities in patients with connective tissue diseases

Quantitative analysis of nailfold capillary abnormalities in patients with connective tissue diseases

Aerosolized Iloprost Therapy Could Not Replace Long-term IV Epoprostenol (Prostacyclin) Administration in Severe Pulmonary Hypertension

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

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