Novel antagonist implicates the CB1 cannabinoid receptor in the hypotensive action of anandamide

In anaesthetised rats, the endogenous cannabinoid anandamide has potent cardiovascular effects that include a brief pressor effect and a more prolonged depressor response. The depressor response is attenuated after transection of the cervical spinal cord or blockade of alpha-adrenergic receptors by phentolamine, and is dose-dependently inhibited by a selective antagonist of the CB1 cannabinoid receptor. The pressor component is not affected by any of these interventions. This suggests that the depressor response is due to inhibition of sympathetic tone mediated by CB1 receptors, whereas the pressor component is due to a peripheral action that does not involve the same receptors or the sympathetic nervous system.