Cardiovascular actions of cannabinoids

Michael Randall. University of Nottingham, Nottingham, United Kingdom.

Over the last decade there has been significant interest in the cardiovascular actions of both endogenous and phytocannabinoids. This area of research stems from initial studies in isolated blood vessels, which reported that anandamide was a vasorelaxant. Since these initial reports much work has been carried out to elucidate the mechanisms of vasorelaxation to endocannabinoids (see Randall et al., 2004). To date it has been established that the vascular actions of cannabinoids vary between vascular beds and also the location within a specific bed and mechanisms which have been implicated include: release of endothelium-derived autacoids such as nitric oxide and the endothelium-derived hyperpolarizing factor, activation of a novel endothelial cannabinoid receptor, endothelium-dependent metabolism, activation of sensory nerves via TRPV receptors and inhibition of calcium channels, and the participation of cannabinoid CB1 and CB2 receptors. Adding complexity to the vascular actions of cannabinoids, it has also become apparent that phytocannabinoids and synthetic cannabinoid may have different targets compared to those acted on by endocannabinoids. Furthermore, the metabolism of endocannabinoids may either terminate their actions or produce vasoactive metabolites.

More recently we have also shown that activation of peroxisome proliferator-activated receptor gamma (PPARγ) may also contribute to some of the vascular actions of cannabinoids in the medium term (O’Sullivan et al., 2005).

The mechanisms of action identified in isolated blood vessels have not been straightforwardly transferred to the in vivo situation, as there are now a range of conflicting studies which point to both depressor and pressor actions (see Randall et al., 2004). Whilst these apparent conflicts are yet to be resolved, the differences may relate to the different experimental settings for example the absence or presence of anaesthesia and prevailing levels of vascular tone. The actions of cannabinoids on the central nervous system are also likely to impact on their in vivo actions.

In addition to our understanding of the cardiovascular studies, other studies have examined their roles in pathophysiology and these include hypertension, cardiovascular shock and atherosclerosis.

O’Sullivan et al. (2005). Biochem. Biophys. Res. Commun. 337, 824-83

Randall et al. (2004). Br. J. Pharmacol., 142, 20-26