The Role of Endothelial Dysfunction in the Connection Between Gut Microbiota, Vascular Injury, and Arterial Hypertension

The management of arterial hypertension, as recently defined by the European Society of Hypertension, is far from being completely achieved, and further studies are required both in the area of pathophysiology of elevated blood pressure and in developing novel and more effective therapeutic strategies. Recent studies highlighted the primary role of vascular endothelial cells (ECs) played in regulating vascular tone (mostly via nitric oxide release) and counteracting atherothrombosis. On the other hand, endothelial dysfunction, which occurs early in disease states characterized by metabolic disorders (diabetes mellitus, Metabolic Syndrome, dyslipidemias, etc.), represents the key mechanism underlying the loss of the capacity to modulate blood pressure and inhibit smooth cell proliferation as a consequence of a chronic inflammatory condition and oxidative stress. Mounting evidence suggests that there is a substantial contribution to this process accompanying altered microbiota. This occurs via an enhanced endotoxin migration from the epithelial intestinal barrier (LPS in particular), which leads to low-grade endotoxemia. This, in turn, is associated with increased cytokine release, dysregulation of NO synthases, and COX-2 activation, leading to impaired vascular control and elevation of blood pressure. Moreover, the reduced production of antihypertensive metabolites (Short Chain Fatty Acids; SCFA) and the increased production of toxic substances (TMAO), as a consequence of dysbiosis, further potentiate the role of altered microbiota in the development of cardiovascular impairment and arterial hypertension. This chapter aims to assess the pathophysiological mechanisms underlying dysbiosis as a central mechanism associated with vascular impairment and high blood pressure.