Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension
Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive r...
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2021
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oai:doaj.org-article:774e252271d24492b51f6bf46136cf342021-11-25T18:39:30ZVasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension10.3390/ph141111201424-8247https://doaj.org/article/774e252271d24492b51f6bf46136cf342021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1120https://doaj.org/toc/1424-8247Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive rats (SHR). CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in response to acetylcholine in the aortas and G3 of DOCA-salt rats and SHR. The enhancement of vasorelaxation was prevented by the inhibition of nitric oxide (NO) with L-NAME and/or the inhibition of cyclooxygenase (COX) with indomethacin in the aortas and G3 of DOCA-salt and SHR, respectively. The mechanism of the CBD-mediated improvement of endothelial function in hypertensive vessels depends on the vessel diameter and may be associated with its NO-, the intermediate-conductance calcium-activated potassium channel- or NO-, COX-, the intermediate and the small-conductance calcium-activated potassium channels-dependent effect in aortas and G3, respectively. CBD increased the vascular expression of the cannabinoid CB<sub>1</sub> and CB<sub>2</sub> receptors and aortic levels of endocannabinoids with vasorelaxant properties e.g., anandamide, 2-arachidonoylglycerol and palmitoyl ethanolamide in aortas of DOCA-salt and/or SHR. In conclusion, CBD treatment has vasoprotective effects in hypertensive rats, in a vessel-size- and hypertension-model-independent manner, at least partly via inducing local vascular changes in the endocannabinoid system.Marta Baranowska-KuczkoHanna KozłowskaMonika KlozaMagdalena KusaczukEwa Harasim-SymborMichał BiernackiIrena KasackaBarbara MalinowskaMDPI AGarticlecannabidiolvascular (endothelial) dysfunctionSHRDOCA-saltendocannabinoidseNOSMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1120, p 1120 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
cannabidiol vascular (endothelial) dysfunction SHR DOCA-salt endocannabinoids eNOS Medicine R Pharmacy and materia medica RS1-441 |
spellingShingle |
cannabidiol vascular (endothelial) dysfunction SHR DOCA-salt endocannabinoids eNOS Medicine R Pharmacy and materia medica RS1-441 Marta Baranowska-Kuczko Hanna Kozłowska Monika Kloza Magdalena Kusaczuk Ewa Harasim-Symbor Michał Biernacki Irena Kasacka Barbara Malinowska Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
description |
Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive rats (SHR). CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in response to acetylcholine in the aortas and G3 of DOCA-salt rats and SHR. The enhancement of vasorelaxation was prevented by the inhibition of nitric oxide (NO) with L-NAME and/or the inhibition of cyclooxygenase (COX) with indomethacin in the aortas and G3 of DOCA-salt and SHR, respectively. The mechanism of the CBD-mediated improvement of endothelial function in hypertensive vessels depends on the vessel diameter and may be associated with its NO-, the intermediate-conductance calcium-activated potassium channel- or NO-, COX-, the intermediate and the small-conductance calcium-activated potassium channels-dependent effect in aortas and G3, respectively. CBD increased the vascular expression of the cannabinoid CB<sub>1</sub> and CB<sub>2</sub> receptors and aortic levels of endocannabinoids with vasorelaxant properties e.g., anandamide, 2-arachidonoylglycerol and palmitoyl ethanolamide in aortas of DOCA-salt and/or SHR. In conclusion, CBD treatment has vasoprotective effects in hypertensive rats, in a vessel-size- and hypertension-model-independent manner, at least partly via inducing local vascular changes in the endocannabinoid system. |
format |
article |
author |
Marta Baranowska-Kuczko Hanna Kozłowska Monika Kloza Magdalena Kusaczuk Ewa Harasim-Symbor Michał Biernacki Irena Kasacka Barbara Malinowska |
author_facet |
Marta Baranowska-Kuczko Hanna Kozłowska Monika Kloza Magdalena Kusaczuk Ewa Harasim-Symbor Michał Biernacki Irena Kasacka Barbara Malinowska |
author_sort |
Marta Baranowska-Kuczko |
title |
Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
title_short |
Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
title_full |
Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
title_fullStr |
Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
title_full_unstemmed |
Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension |
title_sort |
vasoprotective endothelial effects of chronic cannabidiol treatment and its influence on the endocannabinoid system in rats with primary and secondary hypertension |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/774e252271d24492b51f6bf46136cf34 |
work_keys_str_mv |
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