Abstract
Simple SummaryNitric 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.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.
Highlights
Cardiovascular diseases (CVD) are the leading cause of death worldwide [1,2]
Among the relaxing factors derived from the endothelium, nitric oxide (NO) stands out, as it has an important role in several pathophysiological processes, such as neurotransmission, blood pressure (BP) control, and inhibition of platelet aggregation [8]
The mechanisms involved in the anti-angina effect induced by organic nitrates include reduction in the preload, which is induced by peripheral vasodilation and, in minor extension, by dilation of the epicardial coronary artery and reduction in systemic BP [143]
Summary
Hypertension remains the central risk factor for cardiovascular diseases [3], and a decrease in blood pressure (BP) induces a drop in cardiovascular risk [4]. It has been shown that endocrine factors, and neural and vascular reflexes, contribute to the development of hypertension and induce an increase in vascular tone [6]. Regulation of vascular tone in the vascular smooth muscle cell (VSMC) is determined by the balance between vasoconstrictor and vasorelaxant factors [7]. Vascular endothelium has an important protective function against cardiovascular diseases, presenting a central function in this protection [9]. We discuss the role of NO in hypertension, highlighting the importance of NO in the regulation of the vascular response and the use of the metalbased drugs that release NO
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