Healthy perivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating blood pressure. Evidence suggests that sympathetic nervous stimulation of PVAT triggers activation of adipocyte beta3-adrenoceptors, and the subsequent release of the vasoactive adipokine adiponectin. In obesity plasma adiponectin is reduced, which may result in a loss of PVAT function and subsequent hypertension. Therefore we examined beta3-adrenoceptor and adiponectin function in the PVAT anti-contractile effect.
Body weight, blood pressure, and blood glucose were measured in control C57 mice, and adiponectin knockout (Adipo-/-) mice. Following sacrifice, electrical field stimulation (EFS) profiles of isolated C57 and Adipo-/- mesenteric and skeletal muscle resistance arteries (<250 μm, ± PVAT) were characterised using wire myography. Sympathetic denervation of PVAT using 6-hydroxydopamine (6-OHDA) was performed. Beta3-adrenoceptor function was investigated using the agonist CL-316,243 and antagonist SR59203A. The role of the adipokine adiponectin was examined using exogenous adiponectin and a blocking peptide for adiponectin receptor 1 (ABP). The concentration of adiponectin secretion upon EFS was measured using an ELISA kit.
Adipo-/- mice exhibit significant elevations in both blood pressure and blood glucose. During EFS of isolated ± PVAT arteries, mesenteric and skeletal muscle PVAT from C57 mice elicited an anti-contractile effect, which was absent in the Adipo-/-. Sympathetic denervation of both mesenteric and skeletal muscle PVAT abolished the anti-contractile effect. Inhibition of beta3-adrenoceptors in C57 mesenteric and skeletal muscle PVAT using SR59230A significantly reduced the anti-contractile effect, however activation of beta3-adrenoceptors in Adipo-/- PVAT using CL-316,243 did not restore function. Application of exogenous adiponectin to C57 mesenteric and skeletal muscle –PVAT arteries caused a significant vasodilation. In ± PVAT arteries, incubation with ABP significantly reduced the anti-contractile effect. Using an ELISA, adiponectin secretion from PVAT upon EFS was significantly reduced when incubated with SR59230A.
These results demonstrate that upon sympathetic stimulation, PVAT from two different vascular beds releases adiponectin via activation of beta3-adrenoreceptors, exerting an anti-contractile effect on the blood vessels. In the absence of adiponectin PVAT anti-contractile function is lost, resulting in hypertension and hyperglycaemia, highlighting the importance of adiponectin in vascular function.
1University of Manchester, Manchester, United Kingdom
2University of Salford, Manchester, United Kingdom