HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Muzaffar, S Articles by Jeremy, J Y Search for Related Content PubMed PubMed Citation Articles by Muzaffar, S Articles by Jeremy, J Y

Acute hypoxia simultaneously induces the expression of gp91^phox and endothelial nitric oxide synthase in the porcine pulmonary artery

The Bristol Heart Institute, University of Bristol, UK

Correspondence to:
Correspondence to:
Dr J Y Jeremy
Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK; j.y.jeremy{at}bris.ac.uk

Background: The effect of hypoxia on the formation of superoxide (O₂^–), the expression of gp91^phox and endothelial NO synthase (eNOS) were studied in pig intact pulmonary artery (PA) segments and PA vascular smooth muscle cells (PAVSMCs) and PA endothelial cells (PAECs).

Methods: Segments and cells were incubated under hypoxic conditions for 2 hours (with or without enzyme inhibitors) and the formation of O₂^– measured spectrophotometrically. Protein expression was assessed using Western blotting and immunocytochemistry.

Results: Hypoxia promoted the formation of O₂^– in PA segments, PAVSMCs and PAECs, an effect inhibited by diphenylene iodonium and apocynin (NAD[P]H oxidase inhibitors). Hypoxia induced O₂^– formation was enhanced by inhibition of eNOS and augmented by endotoxin and cytokines and re-oxygenation. Hypoxia also promoted the expression of gp91^phox and eNOS. In intact PA segments hypoxia induced the expression of nitrotyrosine and eNOS in the endothelium.

Conclusions: The simultaneous upregulation of NAD[P]H oxidase and eNOS in response to hypoxia in the PA results in the simultaneous formation of O₂^–, NO, and ONOO^–. This may represent either a protective mechanism designed to counter the pro-oxidant effect of hypoxia or a novel pathological mechanism underlying the progression of acute respiratory distress syndrome (ARDS).

Abbreviations: AP-1, activator protein-1; ARDS, acute respiratory distress syndrome; DPI, diphenylene iodonium; IL-1, interleukin 1; LPS, lipopolysaccharide; NADPH, reduced nicotinamide-adenine dinucleotide phosphate; NF-B, nuclear factor-kappa B; NO, nitric oxide; NOS, nitric oxide synthase; O₂^–, superoxide; ONOO^–, peroxynitrite; PAECs, pulmonary artery endothelial cells; PAVSMCs, pulmonary artery vascular smooth muscle cells; SOD, superoxide dismutase; TNF-, tumour necrosis factor-; TXA₂, thromboxane A₂

Keywords: nitric oxide; hypoxia; superoxide; pulmonary artery; acute respiratory distress syndrome (ARDS)

This article has been cited by other articles:

				C. D. Fike, J. C. Slaughter, M. R. Kaplowitz, Y. Zhang, and J. L. Aschner Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L881 - L888. [Abstract] [Full Text] [PDF]

				M. Kirsch, B. Kemp-Harper, N. Weissmann, F. Grimminger, and H. H. H. W. Schmidt Sildenafil in hypoxic pulmonary hypertension potentiates a compensatory up-regulation of NO-cGMP signaling FASEB J, January 1, 2008; 22(1): 30 - 40. [Abstract] [Full Text] [PDF]

				N. Shukla, G. D. Angelini, and J. Y. Jeremy Interactive Effects of Homocysteine and Copper on Angiogenesis in Porcine Isolated Saphenous Vein Ann. Thorac. Surg., July 1, 2007; 84(1): 43 - 49. [Abstract] [Full Text] [PDF]

				A. Sturrock, B. Cahill, K. Norman, T. P. Huecksteadt, K. Hill, K. Sanders, S. V. Karwande, J. C. Stringham, D. A. Bull, M. Gleich, et al. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L661 - L673. [Abstract] [Full Text] [PDF]

				J. Q. Liu, I. N. Zelko, E. M. Erbynn, J. S. K. Sham, and R. J. Folz Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox) Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L2 - L10. [Abstract] [Full Text] [PDF]

				R A Dweik Nitric oxide, hypoxia, and superoxide: the good, the bad, and the ugly! Thorax, April 1, 2005; 60(4): 265 - 267. [Full Text] [PDF]