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一氧化氮及其衍生物在心血管治疗中的未来走向如何?

[Which future in cardiovascular therapy for nitric oxide and its derivatives?].

作者信息

Parent M, Dupuis F, Maincent P, Vigneron C, Leroy P, Boudier A

机构信息

Cithéfor, EA 3452, faculté de pharmacie, université de Lorraine, BP 80403, 54001 Nancy cedex, France.

出版信息

Ann Pharm Fr. 2013 Mar;71(2):84-94. doi: 10.1016/j.pharma.2012.12.004. Epub 2013 Jan 23.

Abstract

Nitric oxide (NO) is involved in the regulation of several physiological processes such as vascular homeostasis. Exogenous NO supply offers major therapeutic interest, especially in the treatment of coronary artery disease, ischemic syndromes and other cardiovascular pathologies. Nevertheless, the administration of NO itself is limited by its short half-life. NO prodrugs have been marketed for decades, e.g. organic nitrates for angina pectoris. These prodrugs display undeniable advantages such as angina crisis relief and preconditioning effect. Nevertheless, they suffer from several drawbacks: toxicity, tolerance, endothelial dysfunction exacerbation. These negative effects are related to massive production of reactive species derived from oxygen or nitrogen, which trigger oxidative and nitrosative stress. New NO donors are under development to overcome those disadvantages, among which the S-nitrosothiols family seems especially promising.

摘要

一氧化氮(NO)参与多种生理过程的调节,如血管稳态。外源性一氧化氮供应具有重要的治疗意义,尤其是在治疗冠状动脉疾病、缺血综合征和其他心血管疾病方面。然而,一氧化氮本身的给药受到其半衰期短的限制。一氧化氮前药已经上市数十年,例如用于治疗心绞痛的有机硝酸盐。这些前药具有不可否认的优势,如缓解心绞痛发作和预处理作用。然而,它们也存在一些缺点:毒性、耐受性、内皮功能障碍加重。这些负面影响与大量产生的氧或氮衍生的活性物质有关,这些物质会引发氧化应激和亚硝化应激。正在开发新的一氧化氮供体以克服这些缺点,其中S-亚硝基硫醇家族似乎特别有前景。

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