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Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo
Author(s) -
Persson M.G.,
Agvald P.,
Gustafsson L.E.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14812.x
Subject(s) - vascular resistance , nitric oxide , chemistry , exhaled nitric oxide , adenosine , anesthesia , pharmacology , exhaled air , medicine , blood pressure , lung , biochemistry , toxicology , biology , lung function
1 Direct evidence for nitric oxide (NO) formation from nitroglycerin (GTN) was obtained by measurements of NO concentrations in exhaled air in artifically‐ventilated, pentobarbitone‐anaesthetized rabbits. 2 The concentration of endogenously formed NO was 23 ± 5 parts per billion (p.p.b.). Infusions of GTN (1–100 μg kg −1 min −1 , i.v.) induced dose‐dependent and biphasic increments in exhaled NO and concomitant reductions in systemic blood pressure. 3 Tolerance to the blood pressure reduction developed in parallel with a decrease in GTN‐induced exhaled NO, a pattern which was unaffected by administration of N ω ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME, 30 mg kg −1 ), l ‐cysteine (200 mg kg −1 ), N‐acetylcysteine (200 mg kg −1 ) or glutathione (200 mg kg −1 ). 4 Intravenous infusions of adenosine (0.7 mg ml −1 , 250 μl kg −1 min −1 ) and GTN (1 mg ml −1 , 250 μl kg −1 min −1 ) elicited similar decrements in pulmonary vascular resistance. GTN elicited a substantial increase in exhaled NO (50 ± 10 p.p.b.) whereas adenosine evoked a markedly smaller increase (7 ± 1 p.p.b.). l ‐NAME (30 mg kg −1 , i.v.) abolished NO in exhaled air, and evoked an increase in pulmonary vascular resistance from 116 ± 19 to 147 ± 9 pulmonary vascular resistance units. After l ‐NAME the change in pulmonary vascular resistance induced by adenosine or GTN was increased to a similar degree. However, while the increase in exhaled NO induced by nitroglycerin was unaffected, the response to adenosine was abolished. 5 The present data demonstrate that NO is formed from GTN in vivo . Furthermore, thiol availability, or nitric oxide synthase activity are not limiting factors in the conversion of nitroglycerin to NO in vivo . Finally, pulmonary haemodynamic changes per se do not explain the observed increase in NO upon nitroglycerin infusion.