604 P. Pacher et al.
Fig.2.HemodynamiceffectsofHU-210inanesthetizedrat.RepresentativerecordingsoftheeffectsofHU-210
(30 μg/kg i.v.) on mean arterial pressure (MAP,top panel), cardiac contractility (LVSPand dP/dt;middle panel),
and pressure-volume (PV)relations(bottom panel) in a pentobarbital-anesthetized rat. Thearrowindicates
the injection of the drug. The decrease of the amplitude of PV loops and their shift to the right are indicative
of decreased cardiac contractile performance
human volunteers who are not chronic marijuana users is similarly inhibited by
SR141716 (Huestis et al. 2001). In healthy young adults, the heart is under dominant
vagal tone, and the tachycardic effect of THC is most likely due to inhibition of
acetylcholine release from cardiac vagal efferents via presynaptic CB 1 receptors
(Szabo et al. 2001).
Acute drug effects on blood pressure are the result of changes in peripheral vas-
cular resistance, cardiac output, or both. Recent unpublished results in the authors’
laboratory, using the pressure-volume conductance system (Pacher et al. 2003 and
2004; Fig. 2) in pentobarbital-anesthetized mice in vivo, indicate that the hypoten-
sive effect of (–)-11-OH-∆^9 -THC dimethylheptyl (HU-210) results primarily from
a decrease in cardiac contractility (Fig. 2). In contrast, anandamide reduces both