Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension

Abstract

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities.

Keywords: arginine; arterial hypertension; cardiovascular disease; chronic disease; endothelial dysfunction; exercise; heart failure; occupational medicine; outcome; rehabilitation.

Figure 1

Effects of endothelial-derived vasoactive mediators in the cross-talk between endothelial and vascular smooth muscle cells. ACE: Angiotensin converting enzyme; ACE2: Angiotensin converting enzyme 2; Ang I: Angiotensin I; Ang II: Angiotensin II; Ang 1-7: Angiotensin 1-7; AT1: Angiotensin II type 1 receptor; MAS: Proto-oncogene G-protein-coupled receptor; eNOS: Endothelial nitric oxide synthase; BH4: Tetrahydrobiopterin; ET-1: Endothelin 1; ET_B1: Endothelin receptor B1; ET_B2: Endothelin receptor B2; ET_A: Endothelin receptor A; NO: Nitric oxide; PGI₂: Prostacyclin; NADPH: Nicotinamide adenine dinucleotide phosphate; ROS: Reactive oxygen species; cGMP: Cyclic guanosine monophosphate; cAMP: Cyclic adenosine monophosphate; IP₃: Inositol triphosphate; DAG: Diacylglycerol; ACE-I: Angiotensin-converting enzyme inhibitors; ARBs: Angiotensin II receptor blockers.

Figure 2

Automatic measurement of flow-mediated dilation (FMD) using a Food and Drug Administration (FDA)-cleared software. 1: Document identifier; 2: mean diameter; 3: shear rate; 4: video window; 5: results and info panel; 6: data exportation. Reproduced with permission from Quipu SRL, Pisa, Italy.