Mg. Persson et al., DETECTION OF NITRIC-OXIDE IN EXHALED AIR DURING ADMINISTRATION OF NITROGLYCERIN IN-VIVO, British Journal of Pharmacology, 111(3), 1994, pp. 825-828
Direct evidence for nitric oxide (NO) formation from nitroglycerin (GT
N) was obtained by measurements of NO concentrations in exhaled air in
artifically-ventilated, pento barbitone-anaesthetized rabbits. 2 The
concentration of endogenously formed NO was 23 +/- 5 parts per billion
(p.p.b.). Infusions of GTN (1-100 mu g kg(-1) min(-1), i.v.) induced
dose-dependent and biphasic increments in exhaled NO and concomitant r
eductions in systemic blood pressure. 3 Tolerance to the blood pressur
e reduction developed in parallel with a decrease in GTN-induced exhal
ed NO, a pattern which was unaffected by administration of N-omega-nit
ro-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 mu kg(-1)
min(-1)) and GTN (1 mg ml(-1), 250 mu l kg(-1) min(-1)) elicited simi
lar decrements in pulmonary vascular resistance. GTN elicited a substa
ntial increase in exhaled NO (50 +/- 10 p.p.b.) whereas adenosine evok
ed 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 pulmonar
y vascular resistance from 116 +/- 19 to 147 +/- 9 pulmonary vascular
resistance units. After L-NAME the change in pulmonary vascular resist
ance induced by adenosine or GTN was increased to a similar degree. Ho
wever, while the increase in exhaled NO induced by nitroglycerin was u
naffected, the response to adenosine was abolished. 5 The present data
demonstrate that NO is formed from GTN in vivo. Furthermore, thiol av
ailability, 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.