Endogenous Nitric Oxide Release by Vasoactive Drugs Monitored in Exhaled Air

• Published in: American journal of respiratory and critical care medicine Vol. 168; no. 1; pp. 114 - 120
• Main Authors: Malmstrom, Rickard E, Tornberg, Daniel C, Settergren, Goran, Liska, Jan, Angdin, Monika, Lundberg, Jon O, Weitzberg, Eddie
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.07.2003; American Lung Association; American Thoracic Society
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Aged; Aged, 80 and over; Anesthesia; Animals; Biological and medical sciences; Bradykinin - administration & dosage; Bradykinin - pharmacology; Breath Tests; Cardiovascular system; Catheters; Dose-Response Relationship, Drug; Drug dosages; Drug Monitoring - methods; Drug Monitoring - standards; Endothelin-1 - administration & dosage; Endothelin-1 - pharmacology; Endothelium; Endothelium, Vascular - drug effects; Female; Fentanyl; Hogs; Humans; Injections, Intravenous; Luminescent Measurements; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Models, Animal; Nitric oxide; Nitric Oxide - analysis; Nitroglycerin - administration & dosage; Nitroglycerin - pharmacology; Ostomy; Pharmacology. Drug treatments; Pulmonary arteries; Pulmonary Wedge Pressure - drug effects; Sensitivity and Specificity; Substance P - administration & dosage; Substance P - pharmacology; Swine; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Vasodilator agents. Cerebral vasodilators; Veins & arteries; Ventilators; Sweden; Human; Expired air; Vasodilator agent; Substance P; vasodilation; Endothelin 1; Biological activity; Endothelium; Pig; endothelin; Vertebrata; Mammalia; Endogenous; Animal; Nitric oxide; Bradykinin; Nitroglycerin; Organic nitrate; Acetylcholine; Artiodactyla; Ungulata
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200302-159OC

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.