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Published ahead of print on April 2, 2003, doi:10.1164/rccm.200302-159OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 114-120, (2003)
© 2003 American Thoracic Society

Original Article

Endogenous Nitric Oxide Release by Vasoactive Drugs Monitored in Exhaled Air

Rickard E. Malmström, Daniel C. Törnberg, Göran Settergren, Jan Liska, Monika Angdin, Jon O. Lundberg and Eddie Weitzberg

Departments of Physiology and Pharmacology, Surgical Sciences, and Thoracic Surgery, Karolinska Institute; and Divisions of Anaesthesiology and Intensive Care and Cardiothoracic Anaesthetics and Intensive Care, Karolinska Hospital, Stockholm, Sweden

Correspondence and requests for reprints should be addressed to Eddie Weitzberg, M.D., Ph.D., Department of Surgical Sciences, Karolinska Institute, S-17176 Stockholm, Sweden. E-mail: eddie.weitzberg{at}ks.se

Direct measurements of endogenous nitric oxide (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 after intravenous injections of various endothelium-dependent and endothelium-independent vasoactive drugs, in anesthetized pigs and humans. In pigs, a dose-dependent release of exhaled NO was observed for acetylcholine (ACh), bradykinin, substance P, endothelin (ET)-1, and nitroglycerine. Each compound had an individual and highly reproducible release pattern. Bradykinin-induced NO release was enhanced by angiotensin converting enzyme inhibition. ET receptor antagonism markedly reduced the response in exhaled NO to ET-1, whereas atropin abolished the NO response to ACh. NO synthase inhibition abolished basal levels of exhaled NO as well as the responses in exhaled NO to all compounds except nitroglycerine. In humans, ACh evoked a dose-dependent increase of NO levels in exhaled air. NO release by endogenous vasoactive agonists can be measured online in the exhaled air of pigs and humans. 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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