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

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.

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension

“…When NO diffuses to the luminal side of the endothelial monolayer, it exerts an antithrombotic action by inhibiting platelet adhesion and aggregation [ 10 ]. Moreover, NO also prevents leukocyte adhesion to vascular endothelium and leukocyte migration into the vascular wall, thus exerting a physiological anti-atherosclerotic action [ 12 ].…”

Involvement of shedding induced by ADAM17 on the nitric oxide pathway in hypertension

“…Alterations evoked by ADAM17-induced cytokines shedding and other membrane proteins, such as ACE2, may lead to endothelium dysfunction (Kawai et al, 2021), which in turn, induces vascular hemodynamics, endothelial damage, barrier dysfunction, and dysregulation of vascular tonus control, thus changing the vascular environment, leading to cardiovascular incidents (Zhang et al, 1995;Zhang et al, 2020;Da Silva et al, 2021).…”

The Contribution of Gut Microbiota and Endothelial Dysfunction in the Development of Arterial Hypertension in Animal Models and in Humans

“…In fact, in about 90% of cases the precise causes are unknown [ 34 ]. The functioning of the endothelium, the inner layer of blood vessels that controls circulation through the production of vasoactive substances and maintains vascular homeostasis, is one of the first targets in cardiovascular risk factors [ 35 , 36 ]. One of the first diseases associated with the reduced bioavailability of factors released by the endothelium is arterial hypertension, but, from the knowledge available in the scientific literature, it is not possible to determine whether endothelial dysfunction is the cause or a consequence of arterial hypertension [ 37 ].…”