Influence of cannabidiol on vascular function in hypertension

M. Baranowska-Kuczko^1,2, M. Kloza¹, H. Kozłowska¹, M. Toczek¹, B. Malinowska¹. ¹Dep. of Experimental Physiology and Pathophysiology, Medical University of Bialystok, Bialystok, Poland, ²Dep. of Clinical Pharmacy, Medical University of Bialystok, Bialystok, Poland.

Introduction:Cannabidiol has been suggested to be a beneficial treatment of cardiovascular disorders. It directly relaxes human and rat arteries and augments endothelial function in Zucker diabetic fatty rats¹. The aim of the study was to determine the influence of cannabidiol on vascular function in hypertensive rats.

Methods: Experiments were performed in the isolated endothelium-intact thoracic aortae isolated from male spontaneously (SHR) or deoxycorticosterone acetate and high salt-diet treated (DOCA-salt) hypertensive Wistar rats or their appropriate normotensive controls Wistar Kyoto (WKY) or uninephrectomized Wistar (UNX) rats using organ bath technique². Aortae were incubated for 2h with cannabidiol (10 μM) or vehicle (10 μl), then cumulative concentration-response curves were conducted: (1) to acetylcholine (0.0001 - 3 μM) in phenylephrine pre-constricted aortae and (2) to phenylephrine (0.0001 - 30 μM) and a thromboxane A₂ analog U46619 (0.0001 - 3 μM). In each individual preparation only one experimental curve was determined. Results are shown as means ± SEM of n animals as (1) % of relaxation of phenylephrine (10 μM)-induced contraction or (2) % of contraction of KCl (60 mM)-induced tone, respectively. Statistical comparisons were made using Student's unpaired t-test. P<0.05 was considered as significant.

Results: Cannabidiol by itself did not change basal tone but its incubation increased potency of acetylcholine-induced vasorelaxation without changes in maximal response in both model of hypertension but not in respective normotensive strains when compared to vehicle-treated artery (Table 1). Treatment with cannabidiol attenuated the phenylephrine- and U46619-induced vasoconstrictor potency (Table 1). The maximal response was reduced only in phenylephrine-evoked vasoconstriction in normo- and hypertensive animals; R_max (cannabidiol vs vehicle): WKY 52.5±3.7 vs 79.8±2.5; SHR 54.7±4.2 vs 74.5±3.1; UNX 51.6±3.9 vs 82.8±4.0; DOCA-salt 82.4±2.3 vs 92.3±2.7, P<0.05.

Conclusions: The beneficial effect of cannabidiol in hypertension (model-independently) may be partially due to improved endothelium-dependent vasorelaxation and/or reduced vasoconstriction.

References:

1. Wheal AJ et al. (2017). Front Pharmacol 8:248.

2. Baranowska-Kuczko M et al. (2016). Life Sci 151:288-299.

Supported by grants from the National Science Centre (Poland) (No 2015/19/B/NZ7/02270) and the Medical University of Białystok (N/ST/ZB/16/005/2213)