Comparisons between perivascular adipose tissue and the endothelium in their modulation of vascular tone

Abstract

The endothelium is an established modulator of vascular tone; however, the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat, which surrounds many blood vessels, can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in the modulation of vascular tone. Endothelial dysfunction is a hallmark of many vascular diseases, including hypertension and obesity. Moreover, PVAT dysfunction is now being reported in several cardio-metabolic disorders. Thus, this review will also discuss the mechanistic insights into endothelial and PVAT dysfunction in order to evaluate whether PVAT modulation of vascular contractility is similar to that of the endothelium in health and disease.

Linked articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

Figure 1

The vasodilating factors released by the endothelium and PVAT. The conversion of L‐arginine into NO by endothelial (e) NOS in both the endothelium and PVAT stimulate soluble guanylyl cycles (sGC) in the VSM, which in turn converts GTP into cGMP. PKG activation leads to vasorelaxation. The enzymatic activity of COX leads to PGI₂ production within the endothelium and PVAT. Endothelial PGI₂ stimulates AC, which converts ATP into cAMP. PKA is then activated, which leads to relaxation of the VSM. Increasing levels of cAMP can also activate delayed rectifier potassium channels (K_dr) ATP‐sensitive potassium channels (K_ATP). PVAT‐derived PGI₂ causes relaxation of VSM via an unknown mechanism; however, it is most likely to stimulate AC. H₂O₂ is released by both the endothelium and PVAT and exerts its anti‐contractile effects via sGC activation within the VSM. Endothelial H₂O₂ can also directly activate K_Ca on the VSM. H₂S mediates the anti‐contractile effects of PVAT via voltage‐gated potassium channels (K_V) on VSM. Within the endothelium, H₂S activates small‐conductance (SK_Ca) and intermediate‐conductance (IK_Ca) calcium‐activated potassium as well as K_ATP channels on VSM. Activation of SK_Ca and IK_Ca on the endothelium leads to hyperpolarisation, which can spread to VSM via myo‐endothelial gap junctions. Large‐conductance calcium‐activated potassium channels (BK_Ca) are also thought to mediate the anti‐contractile effect of PVAT.