Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors

SIMPLE SUMMARY: Nitric oxide is an important molecule that performs a variety of functions in our bodies, especially in the cardiovascular system. In certain pathological conditions, such as cardiovascular diseases, including hypertension, there is reduced production or bioavailability of nitric oxide. Therefore, compounds that deliver nitric oxide, called nitric oxide donors, are clinically useful. In this review, we discuss the physiological role of nitric oxide, and some of the nitric oxide donors and their clinical uses, focusing on the cardiovascular system. Despite the high number of nitric oxide donors and their known efficacy, it is important to understand the similarities and differences among them and how each of them works, as well as to investigate the development of new molecules that may be better than the NO donors in current use. ABSTRACT: Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.