Development of nitric oxide donors for the treatment of cardiovascular diseases.

Nitric oxide (NO) is a molecule that dynamically modulates the physiological functions of the cardiovascular system, which include relaxation of vascular smooth muscle, inhibition of platelet aggregation, and regulation of immune responses. Because a reduced NO level has been implicated in the onset and progression of various disease states, NO is expected to provide therapeutic benefits in the treatment of cardiovascular diseases, such as essential hypertension, stroke, coronary artery disease, atherosclerosis, platelet aggregation after percutaneous transluminal coronary angioplasty, and ischemia/reperfusion injury. To date, pharmacologically active compounds that can release NO within the body, such as organic nitrates and sodium nitroprusside, have been used as therapeutic agents, but their efficacy is significantly limited by their rapid NO release, poor distribution to the target site, toxicity, and induction of tolerance. Therefore, new NO donors with better pharmacological and pharmacokinetic properties would be highly desirable. In this review, recent challenges in the development of new NO donors and NO delivery systems are summarized. Then, future developments of novel NO donors are also discussed in order to optimize NO delivery in the treatment of cardiovascular diseases.