The nitric oxide pathway and possible therapeutic options in pre-eclampsia
The nitric oxide pathway and possible therapeutic options in pre-eclampsia
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DOI：
10.1111/bcp.12301
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发表时间：
2014-08-01
影响因子：
3.4
通讯作者：
Wilkinson, Ian B.
中科院分区：
文献类型：
--
作者：
Johal, Tamanrit;Lees, Christoph C.;Wilkinson, Ian B.
先兆子痫是一种严重的多系统疾病，具有多种临床表现。虽然不是因果关系，但内皮功能障碍和一氧化氮生物利用度降低可能在这种情况的母体和胎儿病理生理学中发挥重要作用。缺乏针对潜在病理生理变化和逆转内皮功能障碍的治疗方式常常导致胎儿医源性早产，导致新生儿发病和死亡，而这种情况本身与短期和长期孕产妇发病和死亡有关。针对一氧化氮可溶性鸟苷酸环化酶途径的各种成分的药物有助于提高一氧化氮的生物利用度。本综述的目的是概述先兆子痫背景下涉及这些治疗方式的临床研究的现状，重点是： 一氧化氮供体，包括有机硝酸盐和 S-亚硝基硫醇； L-精氨酸，NO 的内源性前体；环鸟苷 3', 5'-单磷酸分解抑制剂，包括西地那非；和其他新型 NO 供体代谢抑制剂。概述了每种方式的优点和局限性，并探讨了先兆子痫的既定治疗方案的发展范围。
Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short-and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; L-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3', 5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored.