![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 281, Issue 3, 1030-1037, 1997
Department of Pharmacology and Toxicology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia
Previous studies indicate that the CB1 cannabinoid
receptor antagonist,
N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A), inhibits the anandamide- and
9-tetrahydrocannabinol- (THC) induced hypotension and
bradycardia in anesthetized rats with a potency similar to that
observed for SR141716A antagonism of THC-induced neurobehavioral
effects. To further test the role of CB1 receptors in the
cardiovascular effects of cannabinoids, we examined two additional
criteria for receptor-specific interactions: the rank order of potency
of agonists and stereoselectivity. A series of cannabinoid analogs
including the enantiomeric pair (-)-11-OH-9-THC
dimethylheptyl (+)-11-OH-9-THC dimethylheptyl were
evaluated for their effects on arterial blood pressure and heart rate
in urethane anesthetized rats. Six analogs elicited pronounced and long
lasting hypotension and bradycardia that were blocked by 3 mg/kg of
SR141716A. The rank order of potency was
(-)-11-OH-9-THC dimethylheptyl 
(-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]cyclohexan-1-ol > (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]cyclohexan-1-ol > THC > anandamide (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]cyclohexan-1-ol, which correlated well with CB1 receptor affinity or
analgesic potency (r = 0.96-0.99). There was no hypotension or
bradycardia after palmitoylethanolamine or
(+)-11-OH-9-THC dimethylheptyl. An initial pressor
response was also observed with THC and anandamide, which was not
antagonized by SR141716A. We conclude that the similar rank orders of
potency, stereoselectivity and sensitivity to blockade by SR141716A
indicate the involvement of CB1-like receptors in the
hypotensive and bradycardic actions of cannabinoids, whereas the
mechanism of the pressor effect of THC and anandamide remains unclear.
This article has been cited by other articles:
|
|
 |
|
  M. A. Williams, S. A. Smith, D. E. O'Brien, J. H. Mitchell, and M. G. Garry The group IV afferent neuron expresses multiple receptor alterations in cardiomyopathyic rats: evidence at the cannabinoid CB1 receptor J. Physiol., February 1, 2008; 586(3): 835 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. O'Sullivan, M. D. Randall, and S. M. Gardiner The in Vitro and in Vivo Cardiovascular Effects of {Delta}9-Tetrahydrocannabinol in Rats Made Hypertensive by Chronic Inhibition of Nitric-Oxide Synthase J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 663 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, N. E. Kaminski, and D. H. Wang Endocannabinoid Regulates Blood Pressure via Activation of the Transient Receptor Potential Vanilloid Type 1 in Wistar Rats Fed a High-Salt Diet J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 763 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Benamar, M. Yondorf, J. J. Meissler, E. B. Geller, R. J. Tallarida, T. K. Eisenstein, and M. W. Adler A Novel Role of Cannabinoids: Implication in the Fever Induced by Bacterial Lipopolysaccharide J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1127 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Gelfand and C. P. Cannon Rimonabant: A Cannabinoid Receptor Type 1 Blocker for Management of Multiple Cardiometabolic Risk Factors J. Am. Coll. Cardiol., May 16, 2006; 47(10): 1919 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, N. E. Kaminski, and D. H. Wang VR1-Mediated Depressor Effects During High-Salt Intake: Role of Anandamide Hypertension, October 1, 2005; 46(4): 986 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, S. Batkai, D. Osei-Hyiaman, L. Offertaler, J. Liu, J. Harvey-White, A. Brassai, Z. Jarai, B. F. Cravatt, and G. Kunos Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H533 - H541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Batkai, P. Pacher, D. Osei-Hyiaman, S. Radaeva, J. Liu, J. Harvey-White, L. Offertaler, K. Mackie, M. A. Rudd, R. D. Bukoski, et al. Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension Circulation, October 5, 2004; 110(14): 1996 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Batkai, P. Pacher, Z. Jarai, J. A. Wagner, and G. Kunos Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H595 - H600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pacher, S. Batkai, and G. Kunos Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice J. Physiol., July 15, 2004; 558(2): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Rademacher, S. Patel, F. A. Hopp, C. Dean, C. J. Hillard, and J. L. Seagard Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1570 - H1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Offertaler, F.-M. Mo, S. Batkai, J. Liu, M. Begg, R. K. Razdan, B. R. Martin, R. D. Bukoski, and G. Kunos Selective Ligands and Cellular Effectors of a G Protein-Coupled Endothelial Cannabinoid Receptor Mol. Pharmacol., March 1, 2003; 63(3): 699 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, N. E. Kaminski, and D. H. Wang Anandamide-Induced Depressor Effect in Spontaneously Hypertensive Rats: Role of the Vanilloid Receptor Hypertension, March 1, 2003; 41(3): 757 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Szabo, U. Nordheim, and N. Niederhoffer Effects of Cannabinoids on Sympathetic and Parasympathetic Neuroeffector Transmission in the Rabbit Heart J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 819 - 826. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Garcia Jr., Z. Jarai, F. Mirshahi, G. Kunos, and A. J. Sanyal Systemic and portal hemodynamic effects of anandamide Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G14 - G20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Hillard Endocannabinoids and Vascular Function J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 27 - 32. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. Sharpe and G. Smith Cannabis: Time for Scientific Evaluation of This Ancient Remedy? Anesth. Analg., February 1, 2000; 90(2): 237 - 237. [Full Text] [PDF]
|
|
|
|
|
|
Z. Jarai, J. A. Wagner, S. K. Goparaju, L. Wang, R. K. Razdan, T. Sugiura, A. M. Zimmer, T. I. Bonner, A. Zimmer, and G. Kunos Cardiovascular Effects of 2-Arachidonoyl Glycerol in Anesthetized Mice Hypertension, February 1, 2000; 35(2): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hanus, A. Breuer, S. Tchilibon, S. Shiloah, D. Goldenberg, M. Horowitz, R. G. Pertwee, R. A. Ross, R. Mechoulam, and E. Fride HU-308: A specific agonist for CB2, a peripheral cannabinoid receptor PNAS, December 7, 1999; 96(25): 14228 - 14233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Jarai, J. A. Wagner, K. Varga, K. D. Lake, D. R. Compton, B. R. Martin, A. M. Zimmer, T. I. Bonner, N. E. Buckley, E. Mezey, et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors PNAS, November 23, 1999; 96(24): 14136 - 14141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zimmer, A. M. Zimmer, A. G. Hohmann, M. Herkenham, and T. I. Bonner Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice PNAS, May 11, 1999; 96(10): 5780 - 5785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ledent, O. Valverde, G. Cossu, F. Petitet, J. Aubert, F. Beslot, G. A. Böhme, A. Imperato, T. Pedrazzini, B. P. Roques, et al. Unresponsiveness to Cannabinoids and Reduced Addictive Effects of Opiates in CB1 Receptor Knockout Mice Science, January 15, 1999; 283(5400): 401 - 404. [Abstract] [Full Text]
|
|
|
|
|
|
M. Shen and S. A. Thayer Delta 9-Tetrahydrocannabinol Acts as a Partial Agonist to Modulate Glutamatergic Synaptic Transmission between Rat Hippocampal Neurons in Culture Mol. Pharmacol., January 1, 1999; 55(1): 8 - 13. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Wagner, K. Varga, Z. Jarai, and G. Kunos Mesenteric Vasodilation Mediated by Endothelial Anandamide Receptors Hypertension, January 1, 1999; 33(1): 429 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Varga, J. A. Wagner, D. T. Bridgen, and G. Kunos Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension FASEB J, August 1, 1998; 12(11): 1035 - 1044. [Abstract] [Full Text]
|
|
|
|
|
|
L. De Petrocellis, D. Melck, A. Palmisano, T. Bisogno, C. Laezza, M. Bifulco, and V. Di Marzo The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation PNAS, July 7, 1998; 95(14): 8375 - 8380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mukhopadhyay, B. M. Chapnick, and A. C. Howlett Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2046 - H2054. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
