Exhaled nitric oxide as a marker for organic nitrate tolerance.
Exhaled nitric oxide as a marker for organic nitrate tolerance.
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呼出一氧化氮作为有机硝酸盐耐受性的标志。
DOI：
10.1161/01.cir.89.6.2498
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发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Zapol,WM
中科院分区：
文献类型：
--
作者：
Husain,M;Adrie,C;Ichinose,F;Kavosi,M;Zapol,WM
本研究的目的是证明的发展，有机硝酸盐的生化耐受性，通过测量水平的呼出气体一氧化氮（NO）在羔羊静脉注射（IV）硝酸甘油或硝普钠nitrousside.METHODS和NITROTSIV注射硝酸甘油或硝普钠产生剂量依赖性和持续增加的呼出水平的一氧化氮测定在清醒的羔羊气管造口术的化学发光。静脉输注25 μ g·kg-1·min-1硝酸甘油6小时后，呼出气NO峰值水平显著降低（-53.6 +/-4.9%，平均值+/- SEM，P <0.001），静脉注射硝酸甘油后全身肿胀反应减弱（-52.6 +/-5.9%，P <0.001），但硝普钠没有。在随后的12小时无硝酸甘油期后，呼出气中的NO排泄完全恢复，IV硝酸甘油推注给药后全身肿胀变化恢复至基线。对于IV硝普钠激发，肺NO排泄和全身肿胀反应在整个研究中保持恒定。挑战与IV硝酸甘油，但不是硝普钠在12小时的无硝酸甘油期间导致延迟的生化恢复与各种呼出NO水平和全身性水肿反应的挑战与IV nitroglycerin. CONCLUSION测量呼出NO提供在体内，非侵入性的证据，硝酸甘油的生化耐受性的发展。从肺血管系统呼出的气体中释放的NO减少，伴随着体循环中对硝酸甘油血管舒张的耐受性。
BACKGROUNDThis study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside.METHODS AND RESULTSIV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 micrograms.kg-1.min-1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6 +/- 4.9%, mean +/- SEM, P < .001) and systemic hypotensive responses were attenuated (-52.6 +/- 5.9%, P < .001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin.CONCLUSIONSMeasurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation.