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Effect of adenovirus-mediated gene transfer of nitric oxide synthase on vascular reactivity of rat isolated pulmonary arteries

  • Respiratory System
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Abstract

Aerosol gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) to rat lungs increased NOS expression and activity, and prevented hypoxic pulmonary vasoconstriction (HPV) in vivo. Hereby, we examined the effect of eNOS and iNOS aerosol gene transfer on the endothelium-dependent relaxation (EDR) and on acute HPV in isolated rat pulmonary arteries. Changes in isometric forces were recorded in organ baths for large conduit arteries (diameter 1.8±0.1 mm) and in a wire myograph for small resistance arteries (258±35 μm). Male Wistar rats were randomly aerosolized with adenovirus (Ad) encoding β-galactosidase (control), eNOS, or iNOS. Four days later, exhaled nitric oxide was measured, NOS expression within rat lungs was evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry, vasoconstricting agonist and acetylcholine concentration response curves were generated, and the time course of HPV was recorded. Human eNOS and murine iNOS were expressed within rat lung tissue mostly in parenchyma and endothelial cells. Large arteries isolated from Ad-i, eNOS-aerosolized rats developed lower agonist-induced tension than those of control rats. The first and second contractions of the HPV were smaller in the Ad-i, eNOS-aerosolized rats. Contractions were modestly, but significantly and inversely, related to exhaled NO. Agonist- and hypoxia-induced contractions were even more reduced after eNOS aerosolization. There was no significant effect on EDR and no notable difference between small and large vessels. We conclude that adenovirus (Ad)-mediated NOS gene transfer can counteract both pharmacologically and hypoxia-induced increases in pulmonary vascular tone in isolated rat pulmonary arteries. eNOS seems as efficient as iNOS in regulating pulmonary vascular tone.

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Acknowledgements

The authors thank M. Cauberghs, N. Van Pelt, and H. Gillijns for expert technical assistance. This work was supported by the National Fund for Scientific Research (FWO) grant 1.5650.98N.

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Authors and Affiliations

  1. Department of Pneumology, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Leifu Jiang, Rozenn Quarck, Maurits Demedts & Marion Delcroix

  2. Center for Transgene Technology and Gene Therapy, Katholieke Universiteit Leuven, 3000, Leuven, Belgium

    Stefan Janssens & Peter Pokreisz

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  1. Leifu Jiang
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  2. Rozenn Quarck
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Correspondence to Marion Delcroix.

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Jiang, L., Quarck, R., Janssens, S. et al. Effect of adenovirus-mediated gene transfer of nitric oxide synthase on vascular reactivity of rat isolated pulmonary arteries. Pflugers Arch - Eur J Physiol 452, 213–221 (2006). https://doi.org/10.1007/s00424-005-0028-3

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  • DOI: https://doi.org/10.1007/s00424-005-0028-3

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