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Br J Pharmacol. 2009 Jan;156(1):94-104.

Acute Hypertension Reveals Depressor and Vasodilator Effects of Cannabinoids in Conscious Rats.

Ho WS, Gardiner SM.

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK.

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BACKGROUND AND PURPOSE: The cardiovascular effects of cannabinoids can be influenced by anesthesia and can differ in chronic hypertension, but the extent to which they are influenced by acute hypertension in conscious animals has not been determined.

EXPERIMENTAL APPROACH: We examined cardiovascular responses to intravenous administration of anandamide and the synthetic cannabinoid, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzox azin-6-yl]-1-naphthalenylmethanone (WIN55212-2), in conscious male Wistar rats made acutely hypertensive by infusion of angiotensin II (AII) and arginine vasopressin (AVP). Rats were chronically instrumented for measurement of arterial blood pressure and vascular conductances in the renal, mesenteric and hindquarters beds.

KEY RESULTS: Anandamide dose-dependently decreased the mean arterial blood pressure of rats made hypertensive by AII-AVP infusion, but not normotensive rats. Interestingly, acute hypertension also revealed a hypotensive response to WIN55212-2, which caused hypertension in normotensive animals. The enhanced depressor effects of the cannabinoids in acute hypertension were associated with increased vasodilatation in hindquarters, renal and mesenteric vascular beds. Treatment with URB597, which inhibits anandamide degradation by fatty acid amide hydrolase, potentiated the depressor and mesenteric vasodilator responses to anandamide. Furthermore, haemodynamic responses to WIN55212-2, but not to anandamide, were attenuated by the CB(1) receptor antagonist, AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide].

CONCLUSIONS AND IMPLICATIONS: These results broadly support the literature showing that the cardiovascular effects of cannabinoids can be exaggerated in hypertension, but highlight the involvement of non-CB(1) receptor-mediated mechanisms in the actions of anandamide.

PMCID: PMC2697765, PMID: 19133994 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697765/

 


 

World J Gastroenterol. 2008 Oct 28;14(40):6109-14.

Role of Cannabinoids in Chronic Liver Diseases.

Parfieniuk A, Flisiak R.

Cannabinoids are a group of compounds acting primarily via CB1 and CB2 receptors. The expression of cannabinoid receptors in normal liver is low or absent. However, many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells, as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases. It has been shown that CB1 receptor signaling exerts profibrogenic and proinflammatory effects in liver tissue, primarily due to the stimulation of hepatic stellate cells, whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis. Similarly, CB1 receptor stimulation contributes to progression of liver steatosis. In end-stage liver disease, the endocannabinoid system has been shown to contribute to hepatic encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation, relative peripheral hypotension and probably cirrhotic cardiomyopathy. So far, available evidence is based on cellular cultures or animal models. Clinical data on the effects of cannabinoids in chronic liver diseases are limited. However, recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis. Moreover, controlling CB1 or CB2 signaling appears to be an attractive target in managing liver diseases.

PMCID: PMC2761570, PMID: 18985799 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18985799

 


 

Hypertension. 2008 Oct;52(4):601-7. Epub 2008 Sep 8.

Modulation of the Endocannabinoid System in Cardiovascular Disease: Therapeutic Potential and Limitations.

Pacher P, Mukhopadhyay P, Mohanraj R, Godlewski G, Bátkai S, Kunos G.

Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-9413, USA.

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PMCID: PMC2568884, PMID: 18779440 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18779440