Unger P, Bethume P, Berkenboom G, Degré S
Rev Med Brux. 1989 Mar;10(3):82-8.
The authors emphasize the importance of the phenomenon of vascular tolerance to organic nitrates. Its mechanisms remain controversial but there are compelling evidences supporting the role of the availability of sulfhydryl groups in vascular smooth muscle cells. Nitrate tolerance can be avoided or minimized with dosing strategies that use intermittent administration of nitrates, using the smallest effective dose and providing a nitrate-free interval. The preventive role of N-acetyl-cysteine is briefly discussed as well as the absence of cross-tolerance observed with sydnonimines.
作者强调了血管对有机硝酸盐产生耐受性这一现象的重要性。其机制仍存在争议,但有令人信服的证据支持血管平滑肌细胞中巯基可用性的作用。通过采用间歇性给药、使用最小有效剂量并提供无硝酸盐间隔的给药策略,可以避免或最小化硝酸盐耐受性。文中还简要讨论了N-乙酰半胱氨酸的预防作用以及与西地那非不存在交叉耐受性的情况。