Biochemical Reaction Products of Nitric Oxide as Quantitative Markers of Primary Pulmonary Hypertension

Abstract

Primary pulmonary hypertension (PPH) is a rare and fatal disease of unknown etiology. Inflammatory oxidant mechanisms and deficiency in nitric oxide (NO) have been implicated in the pathogenesis of pulmonary hypertension. In order to investigate abnormalities in oxidants and antioxidants in PPH, we studied intrapulmonary NO levels, biochemical reaction products of NO, and antioxidants (glutathione [GSH], glutathione peroxidase [GPx], and superoxide dismutase [SOD]) in patients with PPH (n = 8) and healthy controls (n = 8). Intrapulmonary gases and fluids were sampled at bronchoscopy. Pulmonary hypertension was determined by right-heart catheterization. NO and biochemical reaction products of NO in the lung were decreased in PPH patients in comparison with healthy controls (NO [ppb] in airway gases: control, 8 +/- 1; PPH, 2.8 +/- 0. 9; p = 0.016; and NO products [microM] in bronchoalveolar lavage fluid [BALF]: control, 3.3 +/- 1.05; PPH, 0.69 +/- 0.21; p = 0.03). However, GSH in the lungs of PPH patients was higher than in those of controls (GSH [microM] in BALF: 0.55 +/- 0.04; PPH, 0.9 +/- 0.1; p = 0.015). SOD and GPx activities were similar in the two groups (p >/= 0.50). Biochemical reaction products of NO were inversely correlated with pulmonary artery pressures (R = -0.713; p = 0.047) and with years since diagnosis of PPH (R = -0.776; p = 0.023). NO reaction products are formed through interactions between oxidants and NO, with the end products of reaction dependent upon the relative levels of the two types of molecules. The findings of the study therefore show that NO and oxidant reactions in the lung are related to the increased pulmonary artery pressures in PPH.

Biomarkers in pulmonary hypertension

“…These divergent results could be explained by methodological differences. When measured in the bronchoalveolar lavage fluid of patients with IPAH, biochemical reaction products of NO (nitrate, nitrite and S-nitrosothiol proteins) are significantly lower than in control patients and correlate inversely with pulmonary artery pressures and duration of PAH [63]. eNO levels increase after initiation of intravenous [64] and inhaled [65] prostacyclin therapy, and also after established treatment with bosentan, a nonselective ET receptor antagonist [62].…”

“…It comes primarily from airway epithelial cells with a component from the pulmonary vasculature [61]. Exhaled NO (eNO) has been shown to be lower in patients with IPAH [62][63][64], although there are conflicting studies that show either no difference in eNO compared with controls [65,66] or an increased level [67]. These divergent results could be explained by methodological differences.…”

Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide

“…Nitrite is typically detected through one of several spectrophotometric methods (Griess reaction) involving fluorimetry, chemiluminescence, or ion chromatography [15][16][17][18][19][20][21][22][23][24][25][26][27][28] . The detection limit of fluorimetric methods is 0.1 μM.…”

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

“…Most studies of NO in PAH patients have measured exhaled NO levels from the lungs in order to assess possible changes in NO synthesis in PAH [284][285][286][287][288][289][290]. NO is relatively stable in the gas phase, allowing for such measurements, whereas the instability of NO in biological �uids means that estimates of NO synthesis from blood measurements are usually done via nitrate/nitrite products derived from NO.…”

“…e majority of studies on exhaled NO in PAH patients report lowered levels when compared with controls [284][285][286][287]289], but two such studies report apparent elevated levels, with one reporting a nonsigni�cant trend [288] and the other signi�cant elevation [290]. Consequently, there appears to be substantial variation in these studies.…”