Nitric oxide generation, tachyphylaxis and cross-tachyphylaxis from nitrovasodilators in vivo

Nitric oxide (NO) increments in exhaled air and changes in mean arterial pr essure of anaesthetised rabbits were measured in order to study the NO gene ration from NO donors and tachyphylaxis in NO formation from nitroglycerin. Continuous infusions of isosorbide dinitrate, isosorbide-5-mononitrate and 3-morpholino-sydnonimine (SIN-1) evoked dose-dependent increases in exhale d NO, paralleled by decrements in mean arterial pressure. Repeated infusion s of nitroglycerin resulted in attenuation (P < 0.01) of the NO increase fr om a given dose. Concurrent infusions of isosorbide dinitrate, isosorbide-5 -mononitrate or nitroglycerin reduced the amount of NO emanating from the b ioconversion of a given dose nitroglycerin as measured in the expired air ( P < 0.01 for all drugs), indicating cross-tachyphylaxis. SIN-1 did not exhi bit such cross-tachyphylaxis. In conclusion, measurements of exhaled NO can be a useful tool for exploration of nitrovasodilator tachyphylaxis. Cross- tachyphylaxis is only shared between some nitrovasodilators and is possibly not due to feedback from the generated NO. (C) 1999 Elsevier Science B.V. All rights reserved.