Endocannabinoids modulate G_q/11 protein-coupled receptor agonist-induced vasoconstriction via a negative feedback...

The endocannabinoid (eCB) system centrally and peripherally regulates cardiovascular parameters, including blood pressure, in health and disease. The relationship between G_q/11 protein-coupled receptor activation, regulation of eCBs release (mainly 2-arachidonoylglycerol) and subsequent CB₁ receptor activation was initially observed in the central nervous system. Here, we review the latest findings from systemic physiological studies which include for the first time data from pulmonary arteries. We present evidence for direct CB₁ -dependent cannabinoid ligand-induced vasorelaxation, vascular expression of eCBs along with their degradation enzymes, and indicate the location of the described interaction.

Endocannabinoids (mainly 2-arachidonoylglycerol), acting via CB₁ receptors, evoke vasodilatory effects and may modulate responses of vasoconstrictors for G_q/11 protein-coupled receptors including angiotensin II, thromboxane A₂ , phenylephrine, noradrenaline in systemic or pulmonary arteries. However, the role of the endothelium in this interaction is not well-established, and the precise vascular location of eCB system components remains unclear, which contributes to discrepancies in the interpretation of results when describing the above-mentioned relationship.

Endocannabinoid's negative feedback is responsible for diminishing agonist-induced vasoconstriction, which may be clinically important in the treatment of arterial and pulmonary hypertension. Further research is required to establish the importance of the eCB system and its downstream signalling pathways.