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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
Kristy D. Lake; Billy R. Martin; George Kunos; ; Károly Varga
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@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
This article has been cited by other articles:
Hohmann, A. G., Tsou, K., Walker, J. M. (1999). Cannabinoid Suppression of Noxious Heat-Evoked Activity in Wide Dynamic Range Neurons in the Lumbar Dorsal Horn of the Rat. J. Neurophysiol. 81: 575-583 [Abstract] [Full Text]
Ishioka, N., Bukoski, R. D. (1999). A Role for N-Arachidonylethanolamine (Anandamide) as the Mediator of Sensory Nerve-Dependent Ca2+-Induced Relaxation. J. Pharmacol. Exp. Ther. 289: 245-250 [Abstract] [Full Text]
Copyright © 1997 by the American Heart Association.