Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release

Baker, Hamidah Abu, Dunn, William R., Daly, Craig and Ralevic, Vera (2017) Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release. Cardiovascular Research . ISSN 1755-3245

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Aims: Electrical field stimulation (EFS) elicits robust sensory neurogenic relaxation responses in the rat isolated mesenteric arterial bed but these responses are absent or difficult to demonstrate in isolated arteries. We believe that this mismatch is due to the absence of perivascular adipose tissue (PVAT) as it is conventionally removed in studies on isolated vessels. We aimed to determine whether sensory nerves are expressed in PVAT, their physiological roles and their possible interactions with PVAT-derived adipokines.

Methods and Results: Using confocal imaging, enzyme immunoassay (EIA), myography, vascular perfusion and multiplex analysis of rat mesenteric arteries, we show that PVAT is crucial for the roles of sensory nerves in control of vasomotor tone and adipokine release. Immunofluorescence double staining showed co-expression of calcitonin gene-related peptide (CGRP; sensory neurotransmitter) and PGP9.5 (neuronal marker) in PVAT of mesenteric arteries. CGRP release from dissected PVAT, measured using EIA, was increased by capsaicin which activates sensory nerves. EFS in both mesenteric arteries and perfused mesenteric arterial beds, with and without PVAT, demonstrated neurogenic relaxation in the presence of PVAT, which was greatly attenuated in preparations without PVAT. Neurogenic relaxation due to EFS was associated with release of leptin in PVAT-intact mesenteric arterial beds, which was abolished in preparations without PVAT. Exposure to low oxygen was associated with an attenuated leptin and adiponectin release, but an increase in IL-6 release, from mesenteric arterial beds. Exogenous leptin augmented relaxation to CGRP in mesenteric arteries.

Conclusions: These data show, for the first time, expression of sensory nerves within PVAT and that PVAT is crucial for sensory neurogenic vasorelaxation and crosstalk with adipocytes leading to leptin release, which may augment CGRP-mediated relaxation; leptin release is abolished after exposure to conditions of reduced oxygenation.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in Cardiovascular Research following peer review. The version of record Hamidah Abu Bakar, PhD, William Robert Dunn, PhD, Craig Daly, PhD, Vera Ralevic, PhD; Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilatation and leptin release. Cardiovascular Research, 2017 cvx062. is available online at:
Keywords: sensory nerves, perivascular adipose tissue, leptin
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
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Depositing User: Eprints, Support
Date Deposited: 07 Apr 2017 08:41
Last Modified: 04 May 2020 18:38

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