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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Autores principales: Marta Baranowska-Kuczko, Hanna Kozłowska, Monika Kloza, Magdalena Kusaczuk, Ewa Harasim-Symbor, Michał Biernacki, Irena Kasacka, Barbara Malinowska
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Publicado: MDPI AG 2021
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spelling 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
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