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Published ahead of print on April 2, 2003, doi:10.1164/rccm.200302-159OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 1, July 2003, 114-120

A more recent version of this article appeared on July 1, 2003
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Submitted on February 4, 2003
Accepted on April 1, 2003

Endogenous nitric oxide release by vasoactive drugs monitored in exhaled air

Rickard E Malmstrom1, Daniel Tornberg2, Goran Settergren3, Jan Liska4, Monica Angdin3, Jon O Lundberg1, and Eddie Weitzberg2*

1 Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden, 2 Anaesthesiology and Intensive Care, Karolinska Hospital, Stockholm, Sweden, 3 Cardiothoracic Anaesthetics and Intensive Care, Karolinska Hospital, Stockholm, Sweden, 4 Thoracic Surgery, Karolinska Institutet, Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: eddie.weitzberg{at}ks.se.

Direct measurements of endogenous NO release is of great interest but difficult to perform in vivo. We hypothesized that endogenous NO release from vasoactive substances would be detectable in exhaled air. Exhaled NO was measured following i.v. injections of various endothelium-dependent and independent vasoactive drugs, in anaesthetized pig and man. In pigs, a dose-dependent release of exhaled NO was observed for acetylcholine, bradykinin, substance P, endothelin-1, and nitroglycerine. Each compound had an individual and highly reproducible release pattern. Bradykinin-induced NO release was enhanced by ACE inhibition. Endothelin receptor antagonism markedly reduced the response in exhaled NO to endothelin-1, while atropin abolished the NO response to acetylcholine. NO synthase inhibition abolished basal levels of exhaled NO as well as the responses in exhaled NO to all compounds except nitroglycerine. In man, acetylcholine evoked a dose-dependent increase of NO levels in exhaled air. NO release by endogenous vasoactive agonists can be measured on-line in exhaled air of pig and man. These novel findings may be useful when characterizing NO release from compounds that interfere with NO synthesis or drugs that act as donors of NO. Moreover, the possibility of using exhaled NO as an indicator of pulmonary endothelial dysfunction merits further studies.
Key words: Acetylcholine, Endothelin, Endothelium, Nitric Oxide, Vasodilation




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