Cowan J C
Int J Cardiol. 1986 Jul;12(1):1-19. doi: 10.1016/0167-5273(86)90094-x.
Nitrates are widely used in anginal prophylaxis. In spite of the fact that the concept of nitrate tolerance was first put forward many years ago, the question of tolerance has remained controversial. There is widespread agreement that tolerance does occur to the effects of nitrates on arterial pressure. In contrast, tolerance to the venous and pulmonary effects is disputed. Similarly, the possibility of tolerance to the antianginal effects remains at issue. In this review, I discuss the factors which may have contributed to conflicting results in different studies, in particular recent findings on the rapidity of onset and reversal of tolerance. Tolerance develops rapidly on initiation of treatment and disappears equally rapidly on its discontinuation. In addition, tolerance appears to be a function of plasma nitrate profile. It is most likely to occur when plasma nitrate levels are constant and least likely when nitrate levels fluctuate. Furthermore, the provision of a daily nitrate free interval may protect against the development of tolerance. I then discuss the implications of these findings for patient management. They suggest that nitrate prophylaxis should not be used continuously, if this can be avoided. Rather, prophylaxis should be tailored to the individual to provide protection at times of maximum susceptibility, while allowing nitrate levels to fall at other times. The adequacy of antianginal protection with drug regimens incorporating a nitrate free interval requires further assessment. Similarly, the possibility that a nitrate free interval might lead to withdrawal effects and exacerbation of angina needs to be excluded.
硝酸盐广泛应用于心绞痛的预防。尽管多年前就首次提出了硝酸盐耐受性的概念，但耐受性问题仍存在争议。人们普遍认为，硝酸盐对动脉血压的作用确实会产生耐受性。相比之下，对静脉和肺部作用的耐受性则存在争议。同样，对抗心绞痛作用产生耐受性的可能性也仍有争议。在这篇综述中，我讨论了可能导致不同研究结果相互矛盾的因素，特别是关于耐受性发生和逆转速度的最新发现。耐受性在治疗开始时迅速发展，在停药时同样迅速消失。此外，耐受性似乎是血浆硝酸盐水平的函数。当血浆硝酸盐水平恒定不变时最有可能发生耐受性，而当硝酸盐水平波动时则最不容易发生。此外，提供每日无硝酸盐间隔期可能预防耐受性的发展。然后我讨论了这些发现对患者管理的影响。这些发现表明，如果可以避免，硝酸盐预防不应持续使用。相反，预防措施应根据个体情况进行调整，以便在最大易感性时期提供保护，同时在其他时间允许硝酸盐水平下降。包含无硝酸盐间隔期的药物方案对抗心绞痛保护的充分性需要进一步评估。同样，需要排除无硝酸盐间隔期可能导致撤药效应和心绞痛加重的可能性。
