In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Published: |
Frontiers Media
2017
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/43898/ |
| _version_ | 1848796791260053504 |
|---|---|
| author | Wheal, Amanda J. Jadoon, Khalid Randall, Michael D. O'Sullivan, Saoirse |
| author_facet | Wheal, Amanda J. Jadoon, Khalid Randall, Michael D. O'Sullivan, Saoirse |
| author_sort | Wheal, Amanda J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:53:35Z |
| format | Article |
| id | nottingham-43898 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:53:35Z |
| publishDate | 2017 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-438982020-05-04T18:46:01Z https://eprints.nottingham.ac.uk/43898/ In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats Wheal, Amanda J. Jadoon, Khalid Randall, Michael D. O'Sullivan, Saoirse 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. Frontiers Media 2017-05-18 Article PeerReviewed Wheal, Amanda J., Jadoon, Khalid, 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 cannabinoid sodium nitroprusside vasorelaxation nitric oxide cyclooxygenase ZDF rats http://journal.frontiersin.org/article/10.3389/fphar.2017.00248/full doi:10.3389/fphar.2017.00248 doi:10.3389/fphar.2017.00248 |
| spellingShingle | cannabinoid sodium nitroprusside vasorelaxation nitric oxide cyclooxygenase ZDF rats Wheal, Amanda J. Jadoon, Khalid Randall, Michael D. O'Sullivan, Saoirse In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title | In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title_full | In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title_fullStr | In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title_full_unstemmed | In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title_short | In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats |
| title_sort | in vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of zucker diabetic fatty rats |
| topic | cannabinoid sodium nitroprusside vasorelaxation nitric oxide cyclooxygenase ZDF rats |
| url | https://eprints.nottingham.ac.uk/43898/ https://eprints.nottingham.ac.uk/43898/ https://eprints.nottingham.ac.uk/43898/ |