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(Hypertension. 1997;29:1204-1210.)
© 1997 American Heart Association, Inc.
Articles |
Cardiovascular Effects of Anandamide in Anesthetized and Conscious Normotensive and Hypertensive Rats
From the Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Correspondence to Dr K. Varga, Department of Pharmacology and Toxicology, Virginia Commonwealth University, PO Box 980613, 410 N 12th St, Richmond, VA 23298. E-mail kvarga{at}gems.vcu.edu
Abstract We previously showed that in anesthetized
rats anandamide elicits bradycardia and a triphasic blood pressure
response: transient hypotension secondary to a vagally mediated
bradycardia, followed by a brief pressor and prolonged depressor
response, the latter two effects being similar to those of
9-tetrahydrocannabinol (THC). The prolonged depressor
but not the pressor response was reduced after 
-adrenergic receptor
blockade or cervical spinal cord transection and was inhibited by the
cannabinoid type 1 (CB1) receptor antagonist
SR141716A, suggesting CB1 receptor–mediated
sympathoinhibition as the underlying mechanism. Here we examined the
relationship between sympathetic tone and the
cardiovascular effects of anandamide by testing these
effects in both conscious and anesthetized, normotensive and
spontaneously hypertensive rats. In urethane-anesthetized
normotensive rats, SR141716A inhibited the prolonged depressor and
bradycardic effects of anandamide and THC with similar potency, whereas
it did not affect the pressor response to either agent. Anandamide
caused similar hypotension in spontaneously breathing and in paralyzed,
mechanically ventilated rats, suggesting that the hypotension is not
secondary to respiratory effects. In conscious normotensive rats,
anandamide elicited transient vagal activation and a brief pressor
response, but the prolonged hypotensive component was absent. SR141716A
potentiated and prolonged the brief pressor response to anandamide,
suggesting that the depressor response may have been masked by an
increased pressor response. All three phases of the anandamide response
were present in both anesthetized and conscious
spontaneously hypertensive rats, and the hypotensive component,
inhibited by SR141716A in both, was more prolonged in the absence (>50
minutes) than the presence (10 to 15 minutes) of
anesthesia. We conclude that anandamide causes a
non–CB1 receptor–mediated pressor and a CB1
receptor–mediated prolonged depressor response. The depressor response
can be elicited in both conscious and anesthetized animals, but
its magnitude depends on preexisting sympathetic tone.
Key Words: hypotension • cannabinoids • blood pressure • heart rate
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