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Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors.
Br J Pharmacol 2006; 149(7):898-908BJ

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.

Authors+Show Affiliations

Liver Unit, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17043671

Citation

Moezi, L, et al. "Anandamide Mediates Hyperdynamic Circulation in Cirrhotic Rats Via CB(1) and VR(1) Receptors." British Journal of Pharmacology, vol. 149, no. 7, 2006, pp. 898-908.
Moezi L, Gaskari SA, Liu H, et al. Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. Br J Pharmacol. 2006;149(7):898-908.
Moezi, L., Gaskari, S. A., Liu, H., Baik, S. K., Dehpour, A. R., & Lee, S. S. (2006). Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. British Journal of Pharmacology, 149(7), pp. 898-908.
Moezi L, et al. Anandamide Mediates Hyperdynamic Circulation in Cirrhotic Rats Via CB(1) and VR(1) Receptors. Br J Pharmacol. 2006;149(7):898-908. PubMed PMID: 17043671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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, Y1 - 2006/10/16/ PY - 2006/10/18/pubmed PY - 2007/2/3/medline PY - 2006/10/18/entrez SP - 898 EP - 908 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 149 IS - 7 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17043671/Anandamide_mediates_hyperdynamic_circulation_in_cirrhotic_rats_via_CB_1__and_VR_1__receptors_ L2 - https://doi.org/10.1038/sj.bjp.0706928 DB - PRIME DP - Unbound Medicine ER -