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Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment., Competing Interests: Disclosures None.

Background: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte β3-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin., Objective: We have investigated the effects of PVAT on vessel diameter in vivo, and the contributions of β3-adrenoceptors and adiponectin., Method: In anaesthetised rats, sections of the intact mesenteric bed were visualised and the diameter of arteries was recorded. Arteries were stimulated with electrical field stimulation (EFS), noradrenaline (NA), arginine-vasopressin (AVP), and acetylcholine (Ach)., Results: We report that in vivo, stimulation of PVAT with EFS, NA, and AVP evokes a local anti-constrictive effect on the artery, whilst PVAT exerts a pro-contractile effect on arteries subjected to Ach. The anti-constrictive effect of PVAT stimulated with EFS and NA was significantly reduced using β3-adrenoceptor inhibition, and activation of β3-adrenoceptors potentiated the anti-constrictive effect of vessels stimulated with EFS, NA, and AVP. The β3-adrenoceptor agonist had no effect on mesenteric arteries with PVAT removed. A blocking peptide for adiponectin receptor 1 polyclonal antibody reduced the PVAT anti-constrictive effect in arteries stimulated with EFS and NA, indicating that adiponectin may be the anti-constrictive factor released upon β3-adrenoceptor activation., Conclusions: These results clearly demonstrate that PVAT plays a paracrine role in regulating local vascular tone in vivo, and therefore may contribute to the modulation of blood pressure. This effect is mediated via adipocyte β3-adrenoceptors, which may trigger release of the vasodilator adiponectin., (© 2019 S. Karger AG, Basel.)

The concept that fat cells could influence the circulation and indeed cardiac function has been in existence for ≥20 years and has gained a wide interest and no less excitement as evidence has accrued to suggest that such effects may be profound enough to explain disease states, such as hypertension and metabolic changes associated with obesity and type II diabetes mellitus. This ATVB in Focus intends to examine our current knowledge in this field, and suggests mechanisms that may be responsible for normal perivascular function and how they become disordered in obesity. There is the tantalizing prospect of developing new therapeutic approaches to keep obese individuals healthy and redesignating type II diabetes mellitus as a vascular disease., (© 2014 American Heart Association, Inc.)

Background and Purpose: In response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT-derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline-induced PVAT anticontractile effect.Experimental Approach: In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer.Key Results: PVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β3 -adrenoceptor agonist, CL-316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv 7 channel inhibition using XE 991 reversed the noradrenaline-induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL-316243, but not phenylephrine, was associated with increased adipocyte-derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L-NMMA. PVAT from eNOS-/- mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process.Conclusions and Implications: We have shown that adipocyte-located β3 -adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte-derived NO. This process is dependent upon Kv 7 channel function. We conclude that adipocyte-derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline. [ABSTRACT FROM AUTHOR]