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

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 tis...

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Main Authors: Baker, Hamidah Abu, Dunn, William R., Daly, Craig, Ralevic, Vera
Format: Article
Published: Oxford University Press 2017
Subjects:
Online Access:https://eprints.nottingham.ac.uk/41815/
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author Baker, Hamidah Abu
Dunn, William R.
Daly, Craig
Ralevic, Vera
author_facet Baker, Hamidah Abu
Dunn, William R.
Daly, Craig
Ralevic, Vera
author_sort Baker, Hamidah Abu
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-418152020-05-04T18:38:33Z https://eprints.nottingham.ac.uk/41815/ Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release Baker, Hamidah Abu Dunn, William R. Daly, Craig Ralevic, Vera 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. Oxford University Press 2017-03-23 Article PeerReviewed 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 sensory nerves perivascular adipose tissue leptin https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvx062 doi:10.1093/cvr/cvx062 doi:10.1093/cvr/cvx062
spellingShingle sensory nerves
perivascular adipose tissue
leptin
Baker, Hamidah Abu
Dunn, William R.
Daly, Craig
Ralevic, Vera
Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title_full Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title_fullStr Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title_full_unstemmed Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title_short Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
title_sort sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilation and leptin release
topic sensory nerves
perivascular adipose tissue
leptin
url https://eprints.nottingham.ac.uk/41815/
https://eprints.nottingham.ac.uk/41815/
https://eprints.nottingham.ac.uk/41815/