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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, may be implicated in the anti-contractile effect of PVAT. Accordingly, we have investigated the effect of sympathetic nerve stimulation (SNS) within PVAT on the anti-contractile effect, and have identified the mechanisms involved.

Design and method:

Electrical field stimulation (EFS) profiles of murine mesenteric arteries (<200 μm, +/-PVAT) were characterised using wire myography (0.1–30 Hz, 20 V, 0.2ms pulse duration, 4 s train duration). To demonstrate the release of an anti-contractile factor, the solution surrounding stimulated exogenous PVAT was transferred to a PVAT denuded vessel. Neural inhibition using tetrodotoxin (TTX, 1 μM), or sympathetic denervation using 6-hydroxydopamine (6-OHDA, 2 μM) were performed. β3-adrenoceptor function was investigated using the agonist CL-316,243 (10 μM) and antagonist SR59203A (100 nM). Noradrenaline transport was studied using nisoxetine (1 μM) and corticosterone (100 μM).


During EFS PVAT elicits a reproducible anti-contractile effect, which is replicated using exogenous PVAT. Solution transfer from stimulated exogenous PVAT to a –PVAT vessel significantly reduced contraction, confirming that stimulated PVAT releases a transferable anti-contractile factor. Neural inhibition using TTX, or sympathetic denervation with 6-OHDA, abolished all anti-contractile activity implicating sympathetic nerves in release of anti-contractile factors. β3-adrenoceptor agonist CL-316,243 enhanced the anti-contractile effect, and β3-adrenoceptor antagonist SR59203A reduced the anti-contractile effect, although the PVAT remains overall anti-contractile. Inhibition of all noradrenaline re-uptake using nisoxetine exhibited the same results as SR59230A, as did inhibition of the specific noradrenaline transporter; organic cation transporter-3 (OCT-3) using corticosterone. Combination of nisoxetine or corticosterone with SR59230A totally abolished the anti-contractile effect. Complete inhibition of the effects of the solution transfer could be achieved by incubation of exogenous PVAT with SR59203A.


These results demonstrate that SNS in PVAT elicits an anti-contractile effect by activation of adipocyte β3-adrenoreceptors, triggering the release of vasodilators, and by transport of noradrenaline back into nerves or adipocytes via OCT-3. This suggests that during SNS, healthy PVAT modulates the effects of noradrenaline. Loss of this function may contribute to the development of hypertension.

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