Cannabigerol as a vasodilatory and blood pressure-lowering agent in spontaneously hypertensive rats

Background Cannabigerol (CBG) is a non-intoxicating compound which exhibits unique properties not yet described for other cannabinoids, among them a potent alpha 2 adrenoceptor (α2AR) agonism. However, unlike other well-studied phytocannabinoids (e.g. cannabidiol – CBD) too little research has still been conducted on the therapeutic potential of CBG, and in particular on its effects on the cardiovascular system. It has been reported that CBG exerts strong antioxidant and anti-inflammatory effects. Moreover, because CBG is an agonist of the α2AR, agonist of the peroxisome proliferator-activated receptor gamma, and antagonist of the receptor for serotonin, it has been speculated that it may have applications in the pharmacotherapy of the metabolic syndrome and its components, particularly hypertension [1]. Purpose Thus, the aim of the study was to evaluate the effect of single administration of CBG on blood pressure (BP) and heart rate (HR) in rats with primary hypertension (spontaneously hypertensive rats, SHR) and their normotensive control (Wistar-Kyoto rats, WKY), as well as the effect of CBG on vascular function (aortas and small mesenteric arteries (sMAs)) in SHR and WKY rats. Methods After anaesthesia, the left femoral vein and left carotid artery were cannulated for administration of CBG (10 mg/kg, i.v.) and for measurement of circulatory parameters, method as described previously [2]. We examined the effect of a single administration of CBG on systolic (SBP), diastolic (DBP) and mean (MBP) BP and HR in SHR and WKY rats. Aortas and sMAs were isolated from SHR and WKY, preconstricted with phenylephrine (Phe) and then the vasorelaxant effect of increasing concentrations of CBG (0.01-30 μM) was studied, method as described previously [3]. Results SHRs had higher basal SBP, DBP and MBP (about 190, 130 and 160 mmHg, respectively) values compared to WKY rats (about 110, 80, and 100 mmHg, respectively). A single administration (i.v.) of CBG at a dose of 10 mg/kg caused a decrease in SBP, DBP, MBP and HR values relative to values before CBG administration by approximately: 15% (p<0.001), 40% (p<0.001), 30% (p<0.001) and 20% (p<0.05), respectively, in WKY rats and by 25% (p<0.001), 30% (p<0.001), 25% (p<0.001) and 15% (p<0.01), respectively, in SHRs. In SHRs, we observed a greater decrease in SBP relative to the WKY group (p<0.05). In WKY rats, CBG (0.01-30 μM), but not its vehicle, caused concentration-dependent full relaxation in Phe-preconstricted endothelium-intact sMA rings. In SHR the vasorelaxant effect of CBG was weaker than in WKY. Conclusions (1) Cannabigerol may have a potential use in the treatment of diseases manifested by excessive vasoconstriction and elevated BP, but evaluation of chronic CBG administration is needed. (2) Since CBG lowers BP and HR in WKY rats, detailed studies should be conducted on its safety in the cardiovascular system.