Role of the central autonomic nervous system in the hypotension and bradycardia induced by (-)-delta 9-trans-tetrahydrocannabinol.

Abstract

Abstract (-)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC), when given intravenously (2 mg kg−1) to cats, produced marked decreases in blood pressure and heart rate which developed gradually and were of prolonged duration. Cervical spinal transection (C1-C2) abolished these effects whereas surgical removal of neurogenic tone to the myocardium selectively eliminated the bradycardia. Bilateral vagotomy alone did not modify the action of Δ9-THC upon heart rate or blood pressure. Recordings of spontaneous sympathetic outflow in the inferior cardiac nerve indicated a rapid reduction in neural discharge rate after Δ9-THC administration. These observations support the hypothesis that Δ9-THC produces a cardiodecellerator and hypotensive effect by acting at some level within the sympathetic nervous system. Experiments conducted to investigate transmission in the superior cervical and stellate ganglia demonstrated that Δ9-THC did not alter ganglionic function. Also, responses to intravenous isoprenaline and noradrenaline were unchanged which suggested that Δ9-THC did not interact with α- or β- adrenoceptors. The possible action of Δ9-THC on central sympathetic structures was investigated by perfusion of Δ9-THC into the lateral cerebral ventricle. Δ9-THC so administered produced a significant reduction in heart rate without a substantial lowering of blood pressure. Tritiated or 14C-Δ9-THC perfused into the lateral ventricle demonstrated that the amount of radioactive compound passing into the peripheral circulation was insignificant and could not account for the decrease in heart rate. The current data are in agreement with the proposal that Δ9-THC produces cardiovascular alterations by an action on the central nervous system which results in a decrease in sympathetic tone.