Cannabinoidergic Regulation of the Functional State of the Heart. The Role of the Autonomic Nervous System

Cannabinoids have been shown to induce long-lasting hypotension and bradycardia, which can be preceded by transient tachycardia and hypertension associated with activation of vanilloid TRPV1 receptors. Prolonged hypotension and bradycardia are consequences of the stimulation of cannabinoid CB1 receptors. Endogenous cannabinoids are not involved in regulating heart rate or arterial blood pressure in intact animals. Cannabinoid-induced bradycardia results from the sympatholytic and vagotonic actions of cannabinoids. Prolonged hypotension results from cannabinoid-induced vasorelaxation. Activation of presynaptic CB1 receptors located on sympathetic terminals innervating the heart and arteries leads to inhibition of noradrenaline release from these terminals. Endogenous cannabinoids have cardioprotective effects in coronary occlusion, inhibiting sympathetic influences on the myocardium. Anandamide, which activates TRPV1 receptors, can induce the Bezold–Jarisch reflex. Stimulation of presynaptic CB1 receptors promotes reductions in CGRP (calcitonin gene-related peptide) release from the afferent terminals of the vagus nerve. Stimulation of vanilloid TRPV1 receptors, conversely, induces CGRP release from the sensory fibers of the vagus nerve. The brainstem nuclei may take part in the cardiovascular effects of cannabinoids seen on i.v. administration of CB agonists.