Induced nitric oxide impairs relaxation but not contraction in endotoxin-exposed rat pulmonary arteries

Christa Boer*, A. B.Johan Groeneveld, Gert Jan Scheffer, Jaap J. De Lange, Nico Westerhof, Pieter Sipkema

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background. Many patients with severe acute lung injury do not respond to nitric oxide (NO) inhalational therapy with alleviation of pulmonary arterial hypertension and hypoxemia, so this treatment remains controversial. Materials and methods. We investigated in endotoxin-exposed Wistar rat pulmonary arteries whether endogenous NO alters contractile and relaxing responses, by electrochemical NO and isometric force measurements. Results. Receptor-independent contraction was similar in control and endotoxin-exposed arteries, while thromboxane analogue (TxA)-dependent contraction was less in the latter. Neither non-selective NO synthase (NOS) inhibition by N G-nitro-l-arginine (l-NA) or selective inducible-NOS2 inhibition by aminoguanidine (AG) improved TxA-induced contraction in endotoxin-exposed arteries. Acetylcholine-induced relaxation was impaired in endotoxin-exposed pulmonary arteries, despite a comparable acetylcholine-induced NO release in control arteries. Additionally, NO solution-induced relaxation of endotoxin-exposed arteries was impaired, but could be improved by l-NA or AG. Application of a phosphodiesterase-insensitive cyclic guanosine monophosphate analogue induced similar relaxation in both control and endotoxin-exposed arteries. Conclusions. Endotoxin-associated NOS2-derived NO is thus associated with impaired NO-mediated relaxation, but does not underlie reduced receptor-mediated pulmonary contractile responses. An increased phosphodiesterase activity may underlie the former, so this route can be explored to replace or improve the effect of inhalational NO therapy in severe sepsis-induced acute lung injury in patients.

Original languageEnglish
Pages (from-to)197-202
Number of pages6
JournalJournal of Surgical Research
Volume127
Issue number2
DOIs
Publication statusPublished - 1 Aug 2005

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