In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

Interview with Sophie Saxton: winner of the FCVB Young Investigators Awards

Sympathetic transmission in perivascular adipose tissue function in health and obesity

Sophie Saxton completed her undergraduate degree in Pharmacology (2013) and Master of Research degree in Cardiovascular Sciences (2014) at the University of Manchester.

Since then she has been working on her PhD in Cardiovascular medicine, studying the role of the sympathetic nervous system in perivascular adipose tissue function.

Healthy perivascular adipose tissue (PVAT) exerts an anti-contractile effect on resistance arteries which is vital in regulating arterial tone.

Activation of β3- adrenoceptors by the neurotransmitter, noradrenaline (NA), may be implicated in the anti-contractile effect of PVAT. In obesity the anti-contractile effect is lost, leading to the development of hypertension.

Accordingly, we have investigated the effect of sympathetic nerve stimulation (SNS) within healthy and obese PVAT on the anti-contractile effect.

Electrical field stimulation (EFS) profiles of healthy C57 mouse mesenteric arteries were characterised using wire myography. During EFS PVAT elicits a reproducible anti-contractile effect. To demonstrate the release of an anti-contractile factor, the solution surrounding stimulated exogenous PVAT was transferred to a PVAT denuded vessel. Post-transfer contractility is significantly reduced confirming that stimulated PVAT releases a transferable anti-contractile factor. Sympathetic denervation of PVAT using 6-hydroxydopamine completely abolished the anti-contractile effect. β3-adrenoceptor antagonist SR59203A reduced the anti-contractile effect, although the fat remained overall anti-contractile.

When the antagonist was used in combination with an OCT-3 inhibitor; corticosterone, the anti-contractile effect was completely abolished, demonstrating that the effect is due to both the release of an anti-contractile factor via β3-adrenoceptor activation, and a result of PVAT acting as a reservoir for NA. The effects of an adiponectin receptor 1 blocking peptide were tested, and the anti-contractile effect was significantly reduced, suggesting that the anti-contractile factor may be adiponectin.

A model of obesity was established, and the EFS profiles of ±PVAT vessels were characterised. The anti-contractile effect was completely absent, and could not be rescued using a β3-adrenoceptor agonist; CL-316,243, suggesting that in obesity these receptors are downregulated.

These results demonstrate the roles of PVAT are two-fold. First of all, SNS in PVAT triggers the release of adiponectin via β3-adrenoceptor activation. Secondly PVAT acts as a reservoir for NA, preventing it from reaching the vessel and causing contraction. In obesity, β3-adrenoceptors may have become downregulated, resulting in a loss of function, and leading to hypertension.