Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis

Yang, Ying‐Ying; Lin, Han‐Chieh; Huang, Yo-Ping; Lee, Tzung-Yan; Hou, Ming‐Chih; Wang, Yingwen; Lee, Fa-Yauh; Lee, Shou‐Dong

doi:10.1042/cs20060260

Cited by 36 publications

(42 citation statements)

References 50 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic treatment with AM251 produced the same vascular effects in conjunction with decreases in hepatic collagen production, transforming growth factor-␤, and several markers of the phospholipase A 2 eicosanoid system (22). The portal hypotensive effect in that study may therefore have been partly mediated by the decreased liver fibrosis in addition to reduced portal venous inflow.…”

Section: Splanchnic Hemodynamicsmentioning

confidence: 64%

“…Anandamide effects in the mesenteric circulation are also very concordant in all studies to date. In supraphysiological doses, it increases superior mesenteric arterial flow in cirrhotic rats without any significant effect in controls, an effect blocked by AM251 or SR141716 preadministration (16,22). During anandamide infusion, BDL mesenteric venules also significantly dilate but less prominently than the arterioles.…”

Section: Splanchnic Hemodynamicsmentioning

confidence: 92%

“…In contrast, Yang et al (22) found no changes on arterial pressure in anaesthetized BDL-cirrhotic rats after acute infusion of sequential doses of AM251 (1, 3, 5, 7 mg/kg). Speculative explanations for this discrepancy include differences in anesthetic and the possibility of reflexive adaptation in arterial pressure after exposure to sequential doses of AM251.…”

Section: Systemic Hemodynamicsmentioning

confidence: 94%

See 2 more Smart Citations

Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Moezi

Gaskari²,

Lee³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Moezi L, Gaskari SA, Lee SS. Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis. Am J Physiol Gastrointest Liver Physiol 295: G649 -G653, 2008. First published August 14, 2008 doi:10.1152/ajpgi.90352.2008.-Cirrhosis is associated with marked cardiovascular disturbances. These include hyperdynamic circulation characterized by reduced peripheral vascular resistance and mean arterial pressure and increased cardiac output. Despite the baseline increase in cardiac output, ventricular responsiveness to stimuli is blunted. A number of cellular signaling pathways have been shown to contribute to these abnormalities, including central nervous system cardiovascular dysregulation and humoral factors such as nitric oxide. Endogenous and exogenous cannabinoids have significant cardiovascular effects. Recent evidence suggests that increased activity of the endocannabinoid system at multiple levels contributes to development of both cardiac and vascular changes in cirrhosis. This brief review surveys recent in vivo and in vitro findings in an attempt to highlight the areas of agreement and areas of controversy in the field. The endocannabinoid system affects key cardiovascular regulators, including the autonomic nervous system, cardiac muscle, and vascular smooth muscle. The interplay among these modes of action further complicates interpretation of the in vivo findings. The broad range of cardiovascular actions of endocannabinoids provides ample opportunities for pharmacological manipulation. At the same time, it increases the possibility of undesirable side effects, which need to be carefully evaluated in long-term studies. portal hypertension; vanilloid; anandamide; cirrhotic cardiomyopathy CIRRHOSIS AND PORTAL HYPERTENSION are associated with cardiovascular abnormalities. The circulation becomes hyperdynamic, defined as increased cardiac output and decreased peripheral vascular resistance and blood pressure. The peripheral vasodilatation is also found in local vascular beds such as the mesenteric/splanchnic, pulmonary, renal, and skeletal muscle. Despite the increased baseline cardiac output, the ventricular contractile response to stimuli is attenuated, a condition termed cirrhotic cardiomyopathy (14). Other features of cirrhotic cardiomyopathy include blunted systolic and diastolic responses to stress, electrophysiological abnormalities, including prolongation of repolarization (increased electrocardiographic QT interval), and cardiac chamber hypertrophy or enlargement (8,14).Both conditions are clinically relevant: hyperdynamic circulation contributes to the pathogenesis of portal hypertension and ascites, whereas cirrhotic cardiomyopathy contributes to poor outcomes following stresses such as liver transplantation and may be involved in the genesis of hepatorenal syndrome (8).Of the regional vascular beds, the splanchnic/mesenteric circulation shows the most significant degree of vasodilatation. Moreover, the vasodilatation in this vascular bed is th...

show abstract

Section: Splanchnic Hemodynamicsmentioning

confidence: 64%

Section: Splanchnic Hemodynamicsmentioning

confidence: 92%

Section: Systemic Hemodynamicsmentioning

confidence: 94%

See 1 more Smart Citation

Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Moezi

Gaskari²,

Lee³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown significant antifibrogenic effects of CBR ligands in liver [22,23,24,26,27,30]. However, the effects of CBR ligands on peritoneal tissue have not been examined in the past until a recent study reported that the CB 2 R agonist was able to reduce the peritoneal macrophage number in a murine peritonitis model induced by thioglycollate, an AGE derivative [36].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have also showed that the CBR plays an important role in liver fibrogenesis [21,22,23,24,25]. Moreover, hepatic fibrosis may be rescued by the knockout of the CB 1 R gene or by administration of the CB 1 R antagonist [24,26,27]. CB 2 R, on the other hand, are located on immune cells and modulate cytokine release [28,29].…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid Receptors as Therapeutic Targets for Dialysis-Induced Peritoneal Fibrosis

et al. 2013

View full text Add to dashboard Cite

Background: Long-term exposure to bioincompatible peritoneal dialysis solutions is frequently complicated with peritoneal fibrosis and ultrafiltration failure. As cannabinoid receptor (CBR) ligands have been reported to be beneficial to ameliorate the process of liver fibrosis, we strove to investigate their therapeutic potential to prevent peritoneal fibrosis. Methods: We used the rat model of peritoneal fibrosis induced by intraperitoneal injection of methylglyoxal and in vitro mesothelial cell culture to test the effects of CBR ligands, including the type 1 CBR (CB₁R) antagonist and the type 2 CBR (CB₂R) agonist. Results: In the methylglyoxal model, both intraperitoneal CB₁R antagonist (AM281) and CB₂R agonist (AM1241) treatment significantly ameliorated peritoneal fibrosis. In addition, CB₁R antagonist was able to alleviate TGF-β₁-induced dedifferentiation of mesothelial cells and to maintain epithelial integrity in vitro. Conclusions: Intraperitoneal administration of CBR ligands (CB₁R antagonist and CB₂R agonist) offers a potential therapeutic strategy to reduce dialysis-induced peritoneal fibrosis and to prolong the peritoneal survival in peritoneal dialysis patients.

show abstract

Role of the Endocannabinoid System in Systems Toxicity

Pistos

Theocharis

2009

General, Applied and Systems Toxicology

View full text Add to dashboard Cite

The scientific knowledge regarding the modulation of the endogenous cannabinoid system and its effect on disease pathophysiology has been significantly improved in the last 20 years. Alterations in the expression of cannabinoid receptors, their main endogenous ligands (arachidonoylethanolamide and 2‐arachidonoylglycerol), and related enzyme levels have been reported in different disease states, suggesting their important regulatory role. The pharmacological effects of synthetic compounds that selectively target the endocannabinoid system, established cause‐effect relationships between endocannabinoids and the progress of several disorders. In this review, the importance of endocannabinoid system modulation and also the aspects of the underlying pathways leading to disease or target organ toxicity are reported.

show abstract

Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis

Cited by 36 publications

References 50 publications

Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Cannabinoid Receptors as Therapeutic Targets for Dialysis-Induced Peritoneal Fibrosis

Role of the Endocannabinoid System in Systems Toxicity

Contact Info

Product

Resources

About