Renin–angiotensin system overactivation in perivascular adipose tissue contributes to vascular dysfunction in heart failure

Abstract

Perivascular adipose tissue (PVAT) dysfunction is associated with vascular damage in cardiometabolic diseases. Although heart failure (HF)-induced endothelial dysfunction is associated with renin-angiotensin system (RAS) activation, no data have correlated this syndrome with PVAT dysfunction. Thus, the aim of the present study was to investigate whether the hyperactivation of the RAS in PVAT participates in the vascular dysfunction observed in rats with HF after myocardial infarction surgery. Wire myograph studies were carried out in thoracic aorta rings in the presence and absence of PVAT. An anticontractile effect of PVAT was observed in the rings of the control rats in the presence (33%) or absence (11%) of endothelium. Moreover, this response was substantially reduced in animals with HF (5%), and acute type 1 angiotensin II receptor (AT1R) and type 2 angiotensin II receptor (AT2R) blockade restored the anticontractile effect of PVAT. In addition, the angiotensin converting enzyme 1 (ACE1) activity (26%) and angiotensin II levels (51%), as well as the AT1R and AT2R gene expression, were enhanced in the PVAT of rats with HF. Associated with these alterations, HF induced lower nitric oxide bioavailability, oxidative stress and whitening of the PVAT, which suggests changes in the secretory function of this tissue. The ACE1/angiotensin II/AT1R and AT2R axes are involved in thoracic aorta PVAT dysfunction in rats with HF. These results suggest PVAT as a target in the pathophysiology of vascular dysfunction in HF and provide new perspectives for the treatment of this syndrome.

Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/oxidative stress

“…Heart rate did not change between groups (Table 1), but both contractile index (+dP/dt) and relaxation velocity (-dP/dt) were reduced in HF post-MI rats (Table 1). Together, as previously published by our group [11,12,19] these results demonstrate that the MI induced by permanent coronary artery occlusion surgery is able to induce morphometric and hemodynamic adjustments, similar to that observed in HF.…”

“…The myocardial infarcted area, ventricular hypertrophy index and lung congestion index were assessed as previously described [11]. Only animals that presented infarcted areas covering between 30 to 50% of the left ventricular surface were included in this study [11,12,19,42]. Barcelona, Spain).…”

“…Indeed, we have previously demonstrated that decreased endotheliumdependent vasodilation in the coronary artery, featured by reduced NO bioavailability is crucial to the onset of HF [11,12]. Furthermore, endothelial dysfunction in peripheral arteries could contribute to systemic vasoconstriction, increased vascular peripheral resistance and enhanced cardiac afterload, which, in turn, contribute to HF development [9,10,15,[17][18][19]. Still, although largely reported in co-occurrence, the onset of endothelial dysfunction in HF remains controversial.…”

Perivascular Adipose Tissue Compensation for Endothelial Dysfunction in the Superior Mesenteric Artery of Female SHRSP.Z-<i>Lepr</i>^<i>fa</i>/IzmDmcr Rats

“…This clinical evidence fits with the findings of experimental models using SHRSP.ZF, which were shown to exhibit ventricular diastolic dysfunction with aging, coincidental to deterioration in PVAT compensatory function and vascular dysfunction [7,16]. Thus, targeting PVAT could help address the pathophysiology of vascular dysfunction in cardiovascular diseases [3,17,18].…”

Guidelines for the measurement of vascular function and structure in isolated arteries and veins

“…In addition, PVAT influences vascular mechanical properties and integrity and cellular composition of the vascular wall. These vasoactive actions of PVAT have been confirmed in many vascular beds and in various species including humans (57-59), rodents (60)(61)(62)(63), mice (64)(65)(66)(67), and swine (68)(69)(70)(71).…”