DETECTION OF NITRIC-OXIDE IN EXHALED AIR DURING ADMINISTRATION OF NITROGLYCERIN IN-VIVO

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.