In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats

Wheal, Amanda J. and Jadoon, Khalid and Randall, Michael D. and O'Sullivan, Saoirse (2017) In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats. Frontiers in Pharmacology, 8 . 248/1-248/9. ISSN 1663-9812

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Abstract

Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also enhance endothelial function.

Experimental approach: Male ZDF rats, or ZDF Lean rats, were treated for 7 days (daily i.p. injection) with either 10mg/kg CBD or vehicle (n D 6 per group). Sections of mesenteric resistance arteries, femoral arteries and thoracic aortae were mounted on a wire myograph, and cumulative concentration-response curves to endothelium-dependent (acetylcholine, ACh, 1 nM–100 mM) or endothelium-independent (sodium nitroprusside, SNP, 1 nM–100 mM) agents were constructed. Multiplex analysis was used to measure serum metabolic and cardiovascular biomarkers.

Key results: Vasorelaxation to ACh was significantly enhanced in mesenteric arteries from CBD-treated ZDF rats, but not ZDF Lean rats. The enhanced vasorelaxation in ZDF mesenteric arteries was no longer observed after COX inhibition using indomethacin or nitric oxide (NO) inhibition using L-NAME. Increased levels of serum c-peptide, insulin and intracellular adhesion molecule-1 observed in the ZDF compared to ZDF Lean rats were no longer significant after 7 days CBD treatment.

Conclusion and implications: Short-term in vivo treatment with CBD improves ex vivo endothelium-dependent vasorelaxation in mesenteric arteries from ZDF rats due to COX- or NO-mediated mechanisms, and leads to improvements in serum biomarkers.

Item Type: Article
Additional Information: This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.
Keywords: cannabinoid, sodium nitroprusside, vasorelaxation, nitric oxide, cyclooxygenase, ZDF rats
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
Identification Number: 10.3389/fphar.2017.00248
Depositing User: Eprints, Support
Date Deposited: 30 Jun 2017 09:31
Last Modified: 23 Jan 2018 21:25
URI: http://eprints.nottingham.ac.uk/id/eprint/43898

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