[Influence of anandamide, the endogenous agonist of cannabinoid receptors on the circulatory system].

Cannabinoids, the active ingredients of Cannabis sativa, have been used by humans as hallucinogens and therapeutic agents for thousands of years. These agents are now known to act through the cannabinoid CB1 and CB2 receptors. The recent discovery of endogenous cannabinoids and the fact that they are involved in the pathology of hypotension associated with hemorrhage, sepsis, cirrhosis, and myocardial infarction indicate that cannabinoids play a greater role in human and animal pathophysiology than initially anticipated. Anandamide is the first of the endogenous cannabinoid ligands discovered. Its intravenous administration produces a characteristic three-phase response in the circulatory systems of experimental animals: In phase 1--a short-lasting decrease in heart rate and systemic blood pressure is related to activation of vanilloid TRPV1 receptors. In phase 2 an increase in blood pressure involves multiple mechanisms, both central (probably through the rostral ventrolateral medulla) and peripheral (vascular, Ca2+-dependent). In phase 3 there is a prolonged decrease in blood pressure and sometimes bradycardia, related to the activation of cannabinoid CB1 and vanilloid TRPV1 receptors. On the basis of this three-phase mechanism, the present paper intends to describe the participation of anandamide in the circulatory system under physiological and pathophysiological conditions. It also discusses the possibility of applying cannabinoid ligands as new therapeutic agents for the treatment of some pathologies.