P11 Role of perivascular adipose tissue AMP-activated protein kinase (AMPK α 1) in regulation endothelium function and no release

Abstract

The endothelium modulates vascular tone through balanced release of vasodilators such as nitric oxide (NO) and vasoconstrictors. AMP-activated protein kinase (AMPK) is expressed throughout the vessel wall as well as in perivascular adipose tissue (PVAT). PVAT, surrounds most blood vessels and secretes substances with vasoactive effects. We have recently demonstrated that AMPK-in PVAT mediates an anticontractile effect on arteries without endothelium. This study investigates the effects of PVAT-derived NO on vascular smooth muscle relaxation and the role of PVAT-AMPK in modulating endothelial function. Aims 1-To study the role of AMPK α 1 in the NO-dependent anticontractile effect of PVAT and eNOS expression in PVAT. 2-To investigate the role of PVAT on endothelial function and vascular contractility. Methodology Thoracic aorta rings, with and without endothelium, from wild-type and AMPK α1 knockout mice were mounted on a wire myograph. Dose–response curves to the AMPK-independent vasodilator cromakalim were studied in vessels contracted with U46619. NO production by thoracic and abdominal PVAT was assessed in conditioned medium using a Sievers NO analyser. The role of NO was studied using the eNOS inhibitor L-NAME, and the levels of total and phosphorylated eNOS in PVAT assessed by immunoblotting. Results 1-PVAT significantly augmented relaxation to cromakalim in WT rings with and without endothelium. 2-Thoracic-PVAT tended to release more NO than abdominal-PVAT. KO mouse PVAT produced significantly less NO. 3- In denuded rings with intact PVAT, L-NAME augmented U46619-induced contraction in WT and KO thoracic rings but not abdominal rings. Conclusion Our data revealed that In WT mice, PVAT modulates endothelial function and augments relaxation through secreting vasoactive molecules such as NO. In addition, thoracic PVAT, containing largely brown adipocytes, produces more NO than abdominal PVAT (white adipocytes). PVAT from AMPK α1 knockout mice produces less NO than WT, and that indicates AMPK α1 has a significant role in PVAT-mediated NO release.