Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat.
Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002188:Cannabis / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D013759:Dronabinol; D012110:Reserpine