Abstract
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 CB1 and CB2 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.
Highlights
We used two hypertension models with different etiologies, but both were associated with vascular target-organ damage, including vascular dysfunction and remodeling [9,32]: (1) genetic spontaneously hypertensive rats (SHR) resembling the hypertensive phenotypes of human hypertension, used for the screening of antihypertensive agents [32]; (2) DOCA-salt-induced hypertension with some features of human low-renin hypertension
We revealed changes dependent on the hypertension model, since both KCNN4 and KCNN3 were downregulated in the aortas and mesenteric G3 arteries of SHR, whereas their expression levels were unchanged in DOCA-salt rats, with the exception of the KCNN4 level being enhanced in aortas
We revealed that chronic treatment with CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in a vessel-size- and hypertension-model-independent manner
Summary
Endothelial (vascular) dysfunction is implicated in many diverse human panvascular diseases, including hypertension. It is a multifactorial process characterized mainly by impaired endothelium-dependent vasodilation due to decreased nitric oxide (NO) synthesis and availability, inflammation, increased reactive oxygen species production, vascular remodeling and acute infections, viral diseases [1,2,3]. Pharmacotherapies improving endothelial function with beneficial pleiotropic effects are considered a central target in the treatment of hypertension and other cardiovascular diseases [2,3,4].
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