Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo.
1. Direct evidence for nitric oxide (NO) formation from nitroglycerin (GTN) was obtained by measurements of NO concentrations in exhaled air in artificially-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 micrograms 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 omega-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 microliters kg-1 min-1) and GTN (1 mg ml-1, 250 microliters 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.
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
M G
MG
Persson
P
P
Agvald
L E
LE
Gustafsson
D000111:Acetylcysteine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D005996:Nitroglycerin / Q000378:metabolism* / Q000493:pharmacokinetics*; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D005978:Glutathione; D000241:Adenosine; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine