Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 1038-1042

Increased Lipid Peroxidation in Patients with Pulmonary Hypertension

JEAN-LUC CRACOWSKI, CLAIRE CRACOWSKI, GERMAIN BESSARD, JEAN-LOUIS PEPIN, JANINE BESSARD, CAROLE SCHWEBEL, FRANÇOISE STANKE-LABESQUE, and CHRISTOPHE PISON

Laboratoire de Pharmacologie, and Département de Médecine Aiguë Spécialisée, Grenoble University Hospital, Grenoble, France

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 F₂ type III (iPF₂-III), an F₂-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF₂-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF₂-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 iPF₂-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 iPF₂-III levels. This study shows that oxidative stress is increased in patients with pulmonary hypertension. Furthermore, iPF₂-III levels inversely correlate to pulmonary vasoreactivity. These observations are consistent with the hypothesis that free radical generation is involved in PHT pathogenesis.

This article has been cited by other articles:

				E. Delannoy, A. Courtois, V. Freund-Michel, V. Leblais, R. Marthan, and B. Muller Hypoxia-induced hyperreactivity of pulmonary arteries: role of cyclooxygenase-2, isoprostanes, and thromboxane receptors Cardiovasc Res, February 1, 2010; 85(3): 582 - 592. [Abstract] [Full Text] [PDF]

				D. Stolz and M. Tamm From the authors Eur. Respir. J., February 1, 2009; 33(2): 452 - 453. [Full Text] [PDF]

				L. J. Janssen Isoprostanes and Lung Vascular Pathology Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 383 - 389. [Abstract] [Full Text] [PDF]

				R. P. Jankov, C. Kantores, J. Pan, and J. Belik Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L233 - L245. [Abstract] [Full Text] [PDF]

				F. Kamezaki, H. Tasaki, K. Yamashita, M. Tsutsui, S. Koide, S. Nakata, A. Tanimoto, M. Okazaki, Y. Sasaguri, T. Adachi, et al. Gene Transfer of Extracellular Superoxide Dismutase Ameliorates Pulmonary Hypertension in Rats Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 219 - 226. [Abstract] [Full Text] [PDF]

				J. B. Snow, V. Kitzis, C. E. Norton, S. N. Torres, K. D. Johnson, N. L. Kanagy, B. R. Walker, and T. C. Resta Differential effects of chronic hypoxia and intermittent hypocapnic and eucapnic hypoxia on pulmonary vasoreactivity J Appl Physiol, January 1, 2008; 104(1): 110 - 118. [Abstract] [Full Text] [PDF]

				C. Liu, T. Tazzeo, and L. J. Janssen Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+ handling and Rho/ROCK signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1177 - L1184. [Abstract] [Full Text] [PDF]

				C. Kantores, P. J. McNamara, L. Teixeira, D. Engelberts, P. Murthy, B. P. Kavanagh, and R. P. Jankov Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L912 - L922. [Abstract] [Full Text] [PDF]

				A. Ogawa, K. Nakamura, H. Matsubara, H. Fujio, T. Ikeda, K. Kobayashi, I. Miyazaki, M. Asanuma, K. Miyaji, D. Miura, et al. Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension Circulation, September 20, 2005; 112(12): 1806 - 1812. [Abstract] [Full Text] [PDF]

				R. E. Girgis, H. C. Champion, G. B. Diette, R. A. Johns, S. Permutt, and J. T. Sylvester Decreased Exhaled Nitric Oxide in Pulmonary Arterial Hypertension: Response to Bosentan Therapy Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 352 - 357. [Abstract] [Full Text] [PDF]

				T. Higenbottam Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease: A Case for Treatment Proceedings of the ATS, April 1, 2005; 2(1): 12 - 19. [Abstract] [Full Text] [PDF]

				L. G. Wood, M. L. Garg, J. L. Simpson, T. A. Mori, K. D. Croft, P. A. B. Wark, and P. G. Gibson Induced Sputum 8-Isoprostane Concentrations in Inflammatory Airway Diseases Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 426 - 430. [Abstract] [Full Text] [PDF]

				I. R. Preston, G. Tang, J. U. Tilan, N. S. Hill, and Y. J. Suzuki Retinoids and Pulmonary Hypertension Circulation, February 15, 2005; 111(6): 782 - 790. [Abstract] [Full Text] [PDF]

				J.-L. Cracowski and O. Ormezzano Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases Eur. Heart J., October 1, 2004; 25(19): 1675 - 1678. [Full Text] [PDF]

				A. Peacock, R. Naeije, N. Galie, and J.T. Reeves End points in pulmonary arterial hypertension: the way forward Eur. Respir. J., June 1, 2004; 23(6): 947 - 953. [Abstract] [Full Text] [PDF]

				R. Bowers, C. Cool, R. C. Murphy, R. M. Tuder, M. W. Hopken, S. C. Flores, and N. F. Voelkel Oxidative Stress in Severe Pulmonary Hypertension Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 764 - 769. [Abstract] [Full Text] [PDF]

				J. Belik, R. P. Jankov, J. Pan, M. Yi, I. Chaudhry, and A. K. Tanswell Chronic O2 exposure in the newborn rat results in decreased pulmonary arterial nitric oxide release and altered smooth muscle response to isoprostane J Appl Physiol, February 1, 2004; 96(2): 725 - 730. [Abstract] [Full Text] [PDF]

				J. D. Morrow and L. J. Roberts The Isoprostanes: Their Role as an Index of Oxidant Stress Status in Human Pulmonary Disease Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S25 - 30. [Abstract] [Full Text] [PDF]

				S. Eddahibi, N. Morrell, M-P. d'Ortho, R. Naeije, and S. Adnot Pathobiology of pulmonary arterial hypertension Eur. Respir. J., December 1, 2002; 20(6): 1559 - 1572. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 642 - 662. [Full Text] [PDF]

				M. C. Walters, A. W. Nienhuis, and E. Vichinsky Novel Therapeutic Approaches in Sickle Cell Disease Hematology, January 1, 2002; 2002(1): 10 - 34. [Abstract] [Full Text]