The mechanisms underlying ethanol-induced cardiovascular dysfunction include changes in vascular contractility and a neurohumoral response. The renin angiotensin system (RAS) is pointed out as one of the main neurohumoral systems linked to oxidative stress since it regulates oxidative and antioxidant pathways. Perivascular adipose tissue (PVAT) surrounds most blood vessels. In physiological condition, PVAT plays an important effect on reducing the contractile response to vasoconstrictor agents. However, in some pathophysiological situations such as arterial hypertension, PVAT becomes dysfunctional and produce an exacerbated amount of reactive oxygen species (ROS), a response that leads to a reduction in its anti-contractile action. The brown adipose tissue, characteristic of the PVAT that surrounds the thoracic aorta, contains multiple lipid droplets and a wide range of mitochondria. If mitochondria become dysfunctional in adipocytes, there may be an increase in the pro-oxidative state through an exaggerated generation of ROS, which may compromise the anticontractile effect of PVAT and tissue homeostasis. Angiotensin (ANG)II has been shown to promote increased production of O2*-, H2O2 and ONOO - and a decrease in the antioxidant enzyme superoxide dismutase (mt-SOD) through the promotion of mitochondrial dysfunction, resulting in pathophysiological changes in the heart, kidney, cells of the vascular smooth muscle and endothelial cells. The consumption of ethanol promotes vascular dysfunction by an increase in ROS generation, resulting in decreased NO bioavailability, endothelial dysfunction, and increased Ca2+ concentration in vascular smooth muscle cells. Part of this redox unbalance occurs via ethanol-induced mitochondria dysfunction, however, whether ethanol-induced vascular injury depends on mitochondria dysfunction in PVAT is still to be studied. Since ethanol is associated with vascular injury and has an oxidant property, we will test the hypothesis that ethanol consumption increases ANGII and AT1 receptors signaling in PVAT leading to mitochondrial dysfunction, ROS production, and loss of anticontractile effect of PVAT. Whether our hypothesis is confirmed, our study will have significative implications on ethanol-induced vascular injury, as well as it will open new therapeutic opportunities for alcoholism-associated cardiovascular risk.
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