Evaluation of the mechanisms involved in perivascular adipose tissue (PVAT) dysfunction in the thoracic aorta of DOCA-salt hypertensive rats: the role of endogenous ouabain

Abstract

For a long time considered only a mechanical protection of blood vessels and adjacent tissues, perivascular adipose tissue (PVAT) has received increasing attention due to research's describing its paracrine role in physiological conditions, involving the release of vasoactive factors, such as adipokines, nitric oxide (NO) and hydrogen sulfide, and their anti-contractile effect. However, PVAT adjustments in cardiometabolic diseases are still the focus of few studies; yet, it has been described that it is dysfunctional in some of them, such as hypertension, atherosclerosis and obesity. In this sense, our laboratory performed vascular reactivity experiments in DOCA-salt hypertensive rats, in order to investigate the mechanisms of vascular damage observed in this disease. Thus, we have observed that the anti-contractile effect of PVAT is reduced in thoracic aorta of DOCA-salt rats; however, this effect is restored in DOCA-salt rats treated with rostafuroxin (an antagonist of the signalosome pathway induced by endogenous ouabain). We have already published that the aforementioned treatment with rostafuroxin is efficient in: decreasing the systolic blood pressure in DOCA-salt rats, increasing the bioavailability of NO and decreasing reactive oxygen-derived species (ROS) production in mesenteric resistance arteries of hypertensive rats. Thus, reducing endothelial dysfunction and vascular damage to these resistance arteries. Therefore, knowing that PVAT has an important effect on the regulation of vascular tone; that it is dysfunctional and morphologically altered in experimental models of hypertension; that the plasma concentration of endogenous ouabain is elevated in models of volume-dependent hypertension - such as DOCA-salt; that rostafuroxin antagonizes the effects of endogenous ouabain; and that preliminary results indicate that endogenous ouabain participates in PVAT dysfunction present in the thoracic aorta of DOCA-salt rats, the present project aims to evaluate the cellular signaling mechanisms by which endogenous ouabain induces dysfunction in the thoracic aorta PVAT of DOCA-salt.