Potentiation of anandamide effects in mesenteric beds isolated from bile duct-ligated rats: role of nitric oxide

Moezi, Leila; Rezayat, Mehdi; Samini, Morteza; Shafaroodi, Hamed; Mehr, Shahram Ejtemaie; Ebrahimkhani, Mo R.; Dehpour, Ahmad Reza

doi:10.1016/j.ejphar.2003.12.004

Cited by 20 publications

(19 citation statements)

References 43 publications

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“…and the mesenteric vascular bed was prepared as described in details elsewhere, according to McGregor method (1965) [7]. Briefly the abdominal wall was opened and the superior mesenteric artery was identified, cannulated and gently flushed with modified Krebs-Henseleit solution that was bubbled with a mixture of O 2 and CO 2 (pH: 7.4, T = 37°C).…”

Section: Preparation Of Mesenteric Vascular Bedmentioning

confidence: 99%

Opioid Receptor Blockade Improves Mesenteric Responsiveness in Biliary Cirrhosis

et al. 2008

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Arterial vasodilation with concomitant hyperdynamic circulation is a common finding in cirrhotic subjects. Elevated levels of plasma endogenous opioid peptides have been reported in cholestasis and cirrhosis. Increased opioid peptides contribute to different manifestations of chronic liver disease such as pruritus, ascitis, and hepatic encephalopathy. In this study the potential role of opioid system in cirrhosis-induced vascular hyporesponsiveness was investigated. Bile duct ligated and sham operated animals received daily subcutaneous administration of naltrexone, an opioid receptor antagonist (20 mg/kg/day), or saline for 28 days. After 4 weeks the superior mesenteric artery was cannulated and was perfused according to McGregor method and then phenylephrine vasoconstrictor response of mesenteric vessels (10(-10) to 10(-6 )mol) was examined. In order to evaluate the effects of acute opioid receptor blockade, additional groups of animals were treated by acute single intraperitoneal naltrexone injection (20 mg/kg). Plasma level of nitrite/nitrate as an indicator for nitric oxide production was measured. Biliary cirrhosis was accompanied with a decrease in baseline perfusion pressure in mesenteric vascular bed (P < 0.01). Chronic opioid receptor blockade significantly increased this parameter (P < 0.01). The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P < 0.01). Acute single injection of naltrexone could not influence the understudied homodynamic parameters. Chronic opioid receptor blockade did not modulate the increased nitrite/nitrate levels following cholestasis. This study provided evidence on the contribution of endogenous opioid system to vascular hyporesponsiveness in cirrhosis which is not directly correlated to high plasma NO levels.

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Section: Preparation Of Mesenteric Vascular Bedmentioning

confidence: 99%

Opioid Receptor Blockade Improves Mesenteric Responsiveness in Biliary Cirrhosis

et al. 2008

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“…Although acute L-NAME treatment of mesenteric beds completely blocked the anandamide-induced vasorelaxation in sham-operated rats, this vasorelaxation was still present in the BDL rats. The divergent effects of acute vs. chronic NOS blockade thus makes it difficult to clarify the exact interrelationship of NO and endocannabinoids in the vasodilatation of cholestatic liver disease (17). Another study also demonstrated that isolated mesenteric arteries of CCl 4 -cirrhotic rats are more sensitive to anandamide than control vessels (5).…”

Section: Splanchnic Hemodynamicsmentioning

confidence: 90%

“…Further studies by this group in isolated mesenteric arteries from BDL rats suggested that anandamide mediates its direct vasodilatory effects by activating vascular Ca 2ϩ -dependent potassium channels (24). Anandamide-induced relaxation is also significantly potentiated in phenylephrine-preconstricted mesenteric vascular beds of 7-day BDL rats (17). This is a model of cholestasis with some liver architectural disorganization but no cirrhosis.…”

Section: Splanchnic Hemodynamicsmentioning

confidence: 99%

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

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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...

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“…Anandamide levels were increased due to cirrhosis in the liver, and this was associated with the pathological responses mediated by fibrin-producing stellate cells as well as the vascular endothelium [101,104]. The necrotic cell death associated with endocannabinoids in stellate cells appears to be associated with the accumulation of reactive oxygen species, rather than effects due to CB 1 - or CB 2 -mediated signal transduction [98,99,105].…”

Section: Hepatic Cannabinoid Signalingmentioning

confidence: 99%

Signal Transduction via Cannabinoid Receptors

Dalton

Bass²,

Horn³

et al. 2009

CNSNDDT

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The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are lipid mediators that signal via CB1 and CB2 cannabinoid receptors and Gi/o-proteins to inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase (MAPK). In the brain, CB1 receptors interact with opioid receptors in close proximity, and these receptors may share G-proteins and effector systems. In the striatum, CB1 receptors function in coordination with D1 and D2 receptors, and combined stimulation of CB1-D2 receptor heteromeric complexes promotes a unique interaction to stimulate cAMP production. CB1 receptors also trigger growth factor receptor signaling cascades in cells by engaging in cross-talk or inter-receptor signal transmission with the receptor tyrosine kinase (RTK) family. Mechanisms for CB1 receptor-RTK transactivation can include stimulation of signal transduction pathways regulated by second messengers such as phospholipase C (PLC), metalloprotease cleavage of membrane-bound precursor proteins such as epidermal growth factor which activate RTKs, RTK autophosphorylation, and recruitment of non-receptor tyrosine kinases. CB1 and CB2 receptors are expressed in peripheral tissues including liver and adipose tissue, and are induced in pathological conditions. Novel signal transduction resulting from endocannabinoid regulation of AMP-regulated kinase (AMPK) and peroxisome proliferator-activated receptors (PPARs) have been discovered from studies of hepatocytes and adipocytes. It can be predicted that drug discovery of the future will be based upon these novel signal transduction mechanisms for endocannabinoid mediators.

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Potentiation of anandamide effects in mesenteric beds isolated from bile duct-ligated rats: role of nitric oxide

Cited by 20 publications

References 43 publications

Opioid Receptor Blockade Improves Mesenteric Responsiveness in Biliary Cirrhosis

Opioid Receptor Blockade Improves Mesenteric Responsiveness in Biliary Cirrhosis

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

Signal Transduction via Cannabinoid Receptors

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