Developing New Organic Nitrates for Treating Hypertension: A Review

Nitric oxide (NO) is one of the most important vasodilator molecules produced by endothelium and presents plenty of cardiovascular actions. It has already been established that deficiency in NO/cGMP signaling pathway is involved in pathophysiological mechanisms of many cardiovascular diseases. In this context, the use of NOreleasing drugs 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 applied. Considering that tolerance can occur when these drugs are used 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.