Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB 1 and VR 1 receptors

L. Moezi, S. A. Gaskari, H. Liu, S. K. Baik, A. R. Dehpour, S. S. Lee

Research output: Contribution to journalArticle

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Abstract

Background and purpose:Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB 1 antagonist), AM630 (CB 2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.Experimental approach:Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB 1, CB 2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.Key results:Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB 1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group.Conclusions and implications:These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB 1- and VR1-mediated mechanisms.

Original languageEnglish
Pages (from-to)898-908
Number of pages11
JournalBritish Journal of Pharmacology
Volume149
Issue number7
DOIs
Publication statusPublished - 2006 Dec 9

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Cardiac Output
Superior Mesenteric Artery
Fibrosis
Splanchnic Circulation
Vascular Resistance
Endocannabinoids
Arterial Pressure
Hyperemia
Arterioles
Venules
anandamide
Bile Ducts
Ligation
Western Blotting
Polymerase Chain Reaction
AM 251
capsazepine
iodopravadoline
Proteins
TRPV1 receptor

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Moezi, L. ; Gaskari, S. A. ; Liu, H. ; Baik, S. K. ; Dehpour, A. R. ; Lee, S. S. / Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB 1 and VR 1 receptors. In: British Journal of Pharmacology. 2006 ; Vol. 149, No. 7. pp. 898-908.
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abstract = "Background and purpose:Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB 1 antagonist), AM630 (CB 2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.Experimental approach:Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB 1, CB 2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.Key results:Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB 1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group.Conclusions and implications:These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB 1- and VR1-mediated mechanisms.",
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Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB 1 and VR 1 receptors. / Moezi, L.; Gaskari, S. A.; Liu, H.; Baik, S. K.; Dehpour, A. R.; Lee, S. S.

In: British Journal of Pharmacology, Vol. 149, No. 7, 09.12.2006, p. 898-908.

Research output: Contribution to journalArticle

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T1 - Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB 1 and VR 1 receptors

AU - Moezi, L.

AU - Gaskari, S. A.

AU - Liu, H.

AU - Baik, S. K.

AU - Dehpour, A. R.

AU - Lee, S. S.

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N2 - Background and purpose:Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB 1 antagonist), AM630 (CB 2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.Experimental approach:Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB 1, CB 2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.Key results:Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB 1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group.Conclusions and implications:These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB 1- and VR1-mediated mechanisms.

AB - Background and purpose:Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB 1 antagonist), AM630 (CB 2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.Experimental approach:Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB 1, CB 2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.Key results:Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB 1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group.Conclusions and implications:These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB 1- and VR1-mediated mechanisms.

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