Increased lipid peroxidation in patients with pulmonary hypertension.
Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of isoprostaglandin F(2alpha) type III (iPF(2alpha)-III), an F(2)-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF(2alpha)-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF(2alpha)-III levels were measured by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were investigated for response to inhaled NO challenge. Urinary iPF(2alpha)-III levels in PHT patients (225 +/- 27 pmol/mmol creatinine) were 2.3 times as high as in controls (97 +/- 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial pressure variation and the pulmonary vascular resistance variation in response to inhaled NO were correlated to basal iPF(2alpha)-III levels. This study shows that oxidative stress is increased in patients with pulmonary hypertension. Furthermore, iPF(2alpha)-III levels inversely correlate to pulmonary vasoreactivity. These observations are consistent with the hypothesis that free radical generation is involved in PHT pathogenesis.
Cracowski
J L
JL
Laboratoire de Pharmacologie, and Département de Médecine Aiguë Spécialisée, Grenoble University Hospital, Grenoble, France. Jean-Luc.Cracowski@ujf-grenoble.fr
Cracowski
C
C
Bessard
G
G
Pepin
J L
JL
Bessard
J
J
Schwebel
C
C
Stanke-Labesque
F
F
Pison
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers; D002849:Chromatography, Gas; D003627:Data Interpretation, Statistical; D015237:Dinoprost / Q000652:urine; D005260:Female; D005609:Free Radicals; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015227:Lipid Peroxidation; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage; D018384:Oxidative Stress; D016138:Walking
D015415:Biomarkers; D005609:Free Radicals; D009569:Nitric Oxide; D015237:Dinoprost