The Endothelium in Hypertension: A Short Review
Louise Toledo, Beatriz Domingues Moreno, Andre Fattori, Silvia Elaine Melo, Juan Yugar-Toledo , Heitor Moreno
Laboratory of Cardiovascular Pharmacology & Hypertension, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
*Heitor Moreno, Laboratory of Cardiovascular Pharmacology & Hypertension, School of Medical Sciences,
University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
However, regardless of the mechanisms involved in the pathophysiology of hypertension, it is clear that hypertension is a disease of the small resistance arteries. It is known that in the initial phase, there is a significant impairment of arteriolar vascular tone, and several studies have proven the presence of morphological alterations in the microcirculation of hypertensive patients, characterized by changes in the lumen/wall thickness ratio. However, the proper role of this morphological change is debated: it may be either the cause or the consequence of hypertension, and not all changes seen in hypertensive patients are explained. The most likely hypothesis is the participation of a dynamic mechanism, such as changes in vascular tone (vasoconstriction) or reduction of vasodilation.
Figure 2: Representation of endothelial activation by biochemical and biomechanical stimulation and the smooth muscle cell response. The figure shows endothelial activation mediated by biochemical stimuli (Ang-II, acetylcholine [Ach], histamine [5HT] endothelin-1 [ET-1], adenosine diphosphate [ADP] bradykinin [BK]) and biomechanical stimuli (hydrostatic pressure, cyclic stretching and ‘shear stress’).
Table 1. Endothelial equilibrium by vasoactive and inflammatory factors.
The main molecules synthesized by the endothelium and their vasoactive and hemostatic effects, cell growth modulation and inflammatory actions are presented in Table 1.
The concept of vascular tone regulation came from the works of Furchgott et al., who demonstrated the importance of vascular endothelial integrity in vascular response to acetylcholine and other agonists. Furthermore, the discovery of the central vascular tone modulator, NO, raised the possibility of the participation of ED as an essential mechanism in the pathogenesis of hypertension.
Initial studies conducted in the 1980s investigated the behaviour of endotheliumdependent vasodilation in aorta rings from spontaneously hypertensive and normal rats . At this time, researchers also studied other types of experimental hypertension models, such as deoxycorticosterone acetate (DOCA)-salt-sensitive rats with renovascular hypertension (one clip on the renal artery) and rats with coarctation caused by surgical bandages around the aorta in which reduced vasodilator response to acetylcholine was observed . This change remained even after removing the clip from the kidney artery or the bandages from the aorta, suggesting that the change in endothelial function is secondary to high blood pressure . Similar results were observed in other experimental models [25,26].
In addition, studies with hypertensive patients showed changes in endotheliumdependent vasodilation as a response to acetylcholine infusion and maintenance of endothelium-independent response after the injection of nitrodilators in different vascular beds including the brachial and coronary arteries, and the cutaneous microcirculation [27-30].
Subsequently, the significance of ED as a primary or secondary phenomenon in hypertension was documented by Taddei et al. , who demonstrated alterations in the vasodilating response to acetylcholine in descendants of hypertensive individuals. However, this effect was not observed in children of normotensive subjects. Successively, lower NO bioavailability was demonstrated in the progeny of hypertensive patients compared to those from normotensive individuals.  These observations underlined the participation of ED and reduced NO bioavailability in the pathogenesis of hypertension. These findings were supported by the publication of studies demonstrating antihypertensive drugs' ability to increase NO's bioavailability and restore endothelial function. [33,34]
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