Abstract
The recent acknowledgment of the paracrine role of perivascular adipose tissue (PVAT) in vascular modulation has been supported by many studies investigating major arteries in several animal models and humans. The influence of PVAT on the functional activity of the vascular bed has been a matter of debate, whether it is an anticontractile effect with protective roles or a pro-contractile effect, investigations are underway to address this obscurity. In this investigation, we have studied the effects of vasoconstrictors, phenylephrine and noradrenaline, and vasorelaxants, carbachol and s-nitroso-n- acetylpenicillamine (SNAP), on subclavian and iliac rings with and without PVAT attached; and concentration-response curves were constructed accordingly. Levels of nitric oxide (NO) generated due to activation of the enzyme adenosine monophosphate-activated protein kinase (AMPK) by 5-Aminoimi- dazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) were measured in sub- clavian and iliac PVAT conditioned media. Additionally, Haematoxylin and Eosin staining was performed to analyze and compare the histological characteristics of both arteries. Subclavian and iliac rings with PVAT attached showed stronger contraction to phenylephrine and noradrenaline than that of rings without PVAT attached. At the same time, relaxation tests reported lower relaxation percentages in subclavian and iliac rings with PVAT attached compared to rings without PVAT attached in response to carbachol and SNAP. PVAT treated with AICAR generated higher levels of NO compared to levels of untreated PVAT. Conclusions drawn were the pro-contractile effects demonstrated by the PVAT especially in high concentrations of drugs used. In addition, histology analysis revealed characteristics of white adipose tissue in both PVATs.
Highlights
The perivascular adipose tissue (PVAT) is becoming an important part of the cardiovascular system that plays a significant role in vascular modulation
Subclavian and iliac rings with and without PVAT attached were tested with two vasoconstrictors, phenylephrine and noradrenaline; and responses to a range of concentrations were detected on the myograph in mN and used to construct concentration-response curves, in Figure 3, to demonstrate the effect of PVAT on constriction response
Stronger contractions were produced by the subclavian rings with PVAT in response to noradrenaline compared to phenylephrine
Summary
The perivascular adipose tissue (PVAT) is becoming an important part of the cardiovascular system that plays a significant role in vascular modulation. Described as “The sixth man of the cardiovascular system” by Cheng et al [1], the PVAT is not merely a mechanical support as believed in the past, but is an endocrine organ that regulates and modifies the vascular tone through communication with incoming neuronal signals, interaction with inflammatory mediators, and as a secreting entity that causes contraction/relaxation of the vascular wall. These capabilities make it possible that PVAT will emerge as a potential therapeutic target in controlling vascular responses to different constricting and relaxing drugs, in addition to its possible participation in the underlying causes of atherosclerosis, diabetes mellitus, and cardiovascular diseases. It is less well innervated than BAT, WAT is distributed throughout different tissue depots that store fatty acid molecules as triglycerides and these surround multiple organs to form visceral fat and distribute
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