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.