HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/L11    most recent 00023.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Hampl, V. Articles by Herget, J. Search for Related Content PubMed PubMed Citation Articles by Hampl, V. Articles by Herget, J.

Pulmonary vascular iNOS induction participates in the onset of chronic hypoxic pulmonary hypertension

Václav Hampl,^1,5 Jana Bíbová,^1,5 Alena Baasová,^2,5 Jií Uhlík,³ Dana Miková,^1,5 Olga Hniliková,^1,5 Vra Lachmanová,^4,5 and Jan Herget^1,5

Departments of ¹Physiology, ²Pathophysiology, ³Histology, and ⁴Anesthesiology, Charles University Second Medical School; and ⁵Centre for Cardiovascular Research, Prague, Czech Republic

Submitted 12 January 2005 ; accepted in final form 3 August 2005

Pathogenesis of hypoxic pulmonary hypertension is initiated by oxidative injury to the pulmonary vascular wall. Because nitric oxide (NO) can contribute to oxidative stress and because the inducible isoform of NO synthase (iNOS) is often upregulated in association with tissue injury, we hypothesized that iNOS-derived NO participates in the pulmonary vascular wall injury at the onset of hypoxic pulmonary hypertension. An effective and selective dose of an iNOS inhibitor, L-N⁶-(1-iminoethyl)lysine (L-NIL), for chronic peroral treatment was first determined (8 mg/l in drinking water) by measuring exhaled NO concentration and systemic arterial pressure after LPS injection under ketamine+xylazine anesthesia. A separate batch of rats was then exposed to hypoxia (10% O₂) and given L-NIL or a nonselective inhibitor of all NO synthases, N^G-nitro-L-arginine methyl ester (L-NAME, 500 mg/l), in drinking water. Both inhibitors, applied just before and during 1-wk hypoxia, equally reduced pulmonary arterial pressure (PAP) measured under ketamine+xylazine anesthesia. If hypoxia continued for 2 more wk after L-NIL treatment was discontinued, PAP was still lower than in untreated hypoxic controls. Immunostaining of lung vessels showed negligible iNOS presence in control rats, striking iNOS expression after 4 days of hypoxia, and return of iNOS immunostaining toward normally low levels after 20 days of hypoxia. Lung NO production, measured as NO concentration in exhaled air, was markedly elevated as early as on the first day of hypoxia. We conclude that transient iNOS induction in the pulmonary vascular wall at the beginning of chronic hypoxia participates in the pathogenesis of pulmonary hypertension.

pulmonary circulation; nitric oxide; rat; inducible nitric oxide synthase

This article has been cited by other articles:

				V. Jakoubek, J. Bibova, J. Herget, and V. Hampl Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1638 - H1644. [Abstract] [Full Text] [PDF]

				T. Hoehn, M. William, A. R. McPhaden, H. Stannigel, E. Mayatepek, and R. M. Wadsworth Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis. Eur. Respir. J., June 1, 2006; 27(6): 1311 - 1315. [Abstract] [Full Text] [PDF]