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Effect of chronic ethanol consumption on the modulatory action displayed by perivascular adipose tissue: a role for angiotensin II

Abstract

Chronic ethanol consumption induces significant changes in vascular function and is considered as an important risk factor for the development of cardiovascular diseases, such as hypertension. The following mechanisms were proposed to explain ethanol-induced hypertension: 1) changes in vascular contractility in which ethanol consumption induces endothelial dysfunction and increased vascular contraction; 2) neurohumoral changes in which ethanol consumption promotes activation of the renin-angiotensin system (RAS). In fact, it has been shown that RAS plays a role in ethanol-induced hypertension and vascular dysfunction, thus evidencing the existence of a relationship between the neuroendocrine and myogenic mechanisms that could explain the hypertension associated with ethanol consumption. The perivascular adipose tissue (PVAT) has secretory properties. It releases vasoactive substances (vasorelaxants and vasocontractors) that acting autocrinally, paracrinally or endocrinally modulates the vascular tone. Some pathophysiological condictions, such as hypertension may induce an inflammatory process in PVAT. As a consequence there is a loss of its anti-contractile action resulting from increased production of contractile factors and reduced bioavailability of relaxant factors. Hypertension-induced vascular inflammation is initiated in PVAT and angiotesnin II (ANGII) is an important mediator of this response. ANGII regulates T lymphocyte and macrophage infiltration to PVAT and mediates the production of reactive oxygen species (ROS) and iNOS expression in this tissue. Under physiological conditions, PVAT has a protective and beneficial effect on the regulation of vascular tone, but in non-physiological situations there may be a modification of the anti-contractile phenotype of this tissue that promotes vascular/endothelial dysfunction being these responses time-dependent. However, there are no studies describing the impact of chronic ethanol consumption on the modulatory action exerted by PVAT on vascular tone.Since PVAT plays an important role in regulating vascular function, the present study was designed to investigate the consequences of ethanol consumption on the modulatory action that PVAT exerts on vascular tone. Knowing that changes in PVAT phenotype are time-dependent and that are influenced by different mediators, such as ANGII, we also propose to investigate the effect of ethanol consumption at different time points. We will also investigate the possible participation of ANGII in ethanol-induced changes in PVAT functionality. Our hypothesis is that ANGII, via AT1 receptors activation, will stimulate the recruitment of inflammatory cells that will impair the anti-contractile effect of PVAT by promoting pro-inflammatory cytokine production, adipokine release and ROS production. (AU)