França-Silva Maria S, Balarini Camille M, Cruz Josiane C, Khan Barkat A, Rampelotto Pabulo H, Braga Valdir A
Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58037-760, Brazil.
Health Sciences Center, Federal University of Paraíba, João Pessoa, PB 58037-760, Brazil.
Molecules. 2014 Sep 24;19(9):15314-23. doi: 10.3390/molecules190915314.
Nitric oxide (NO) is one of the most important vasodilator molecules produced by the endothelium. It has already been established that NO/cGMP signaling pathway deficiencies are involved in the pathophysiological mechanisms of many cardiovascular diseases. In this context, the development of NO-releasing drugs for therapeutic use appears to be an effective alternative to replace the deficient endogenous NO and mimic the role of this molecule in the body. Organic nitrates represent the oldest class of NO donors that have been clinically used. Considering that tolerance can occur when these drugs are applied chronically, the search for new compounds of this class with lower tolerance potential is increasing. Here, we briefly discuss the mechanisms involved in nitrate tolerance and highlight some achievements from our group in the development of new organic nitrates and their preclinical application in cardiovascular disorders.
一氧化氮（NO）是内皮产生的最重要的血管舒张分子之一。已经确定，NO/cGMP信号通路缺陷参与了许多心血管疾病的病理生理机制。在这种情况下，开发用于治疗用途的释放NO的药物似乎是一种有效的替代方法，以替代内源性NO不足并模拟该分子在体内的作用。有机硝酸盐是临床上使用的最古老的一类NO供体。考虑到长期使用这些药物时可能会出现耐受性，对这类具有较低耐受性潜力的新化合物的研究正在增加。在这里，我们简要讨论硝酸盐耐受性涉及的机制，并突出我们小组在开发新的有机硝酸盐及其在心血管疾病中的临床前应用方面取得的一些成果。
