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

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.