Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

Beatriz Gálvez-Prieto,Maria S Fernández-Alfonso,Concha F García-Prieto,Reinhold Kreutz,Marta Gil-Ortega,Silvia Arribas,Mariano Ruiz-Gayo,Ana I De Las Heras,Juliane Bolbrinker,Beatriz Somoza,Isabel Aranguez,M Carmen González

doi:10.3389/fphar.2012.00103

Abstract

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

Highlights

Perivascular adipose tissue (PVAT) is considered a highly active endocrine organ that releases a variety of adipokines, inflammatory cytokines, and other factors which influence vascular tone in a paracrine way (Gollasch and Dubrovska, 2004; Gao, 2007)
This study shows that the anticontractile effect of perivascular adipose tissue (PVAT) is absent in spontaneously hypertensive rats (SHR)
Main findings of this study are that (i) leptin production is reduced in periaortic AT from SHR and (ii) that vasodilatory and anticontractile effects of leptin are abolished in SHR aorta

Summary

Introduction

Perivascular adipose tissue (PVAT) is considered a highly active endocrine organ that releases a variety of adipokines, inflammatory cytokines, and other factors which influence vascular tone in a paracrine way (Gollasch and Dubrovska, 2004; Gao, 2007). The lower amount of adipose tissue (AT) facilitates contraction in mesenteric arteries, likely attributable to a diminished paracrine regulation of perivascular fat on mesenteric arterial tone via Kv channels (Gálvez et al, 2006). Periaortic AT from SHR shows a reduced anticontractile effect, probably related to the increase in the number of brown adipocytes and to a reduction in the production of Ang 1–7 (Lu et al, 2011)

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