Age-specific influences of chronic administration of the fatty acid amide hydrolase inhibitor URB597 on cardiovascular parameters and organ hypertrophy in DOCA-salt hypertensive rats

Toczek, Marek; Baranowska-Kuczko, Marta; Grzęda, Emilia; Pędzińska-Betiuk, Anna; Weresa, Jolanta; Malinowska, Barbara

doi:10.1016/j.pharep.2015.10.004

Cited by 29 publications

(27 citation statements)

References 38 publications

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“…Simultaneously, the hypertensive rats were given 1% NaCl in the drinking water with concomitant injections of DOCA (25 mg/kg [18-21] in 0.4 ml/kg DMF). After 4 weeks, half of the normotensive and half of the hypertensive animals were injected with URB597 (1mg/ml/kg) twice a day for the next 2 weeks [12, 22, 23]. At the same time the rest of rats received URB597 solvent – DMSO (1 ml/kg; Tween 80 and 0.9% NaCl (1: 2:7)).…”

Section: Methodsmentioning

confidence: 99%

“…It should be mentioned that fatty acid amide hydrolase (FAAH) is an enzyme, which is responsible for AEA degradation and, therefore, determines endocannabinoids activity in the tissues [10]. Interestingly, studies have shown that both, acute and chronic pharmacological FAAH inhibition by (30-(aminocarbonyl)[1, 10-biphenyl]-3-yl)-cyclohexylcarbamate (URB597) administration normalized elevated blood pressure [11, 12]. Since the ECS controls energy homeostasis [13] we wanted to determine whether decreased FAAH activity would have an impact on cardiac metabolism.…”

Section: Introductionmentioning

confidence: 99%

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The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension

Polak

Harasim-Symbor

Malinowska

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension. Methods: Hypertension was induced by DOCA (25mg/kg) injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg) injections for two weeks. We examined fasting plasma levels of insulin (ELISA), glucose and intramyocardial glycogen (colorimetric method). Expressions of glucose transporters (GLUT1, 4) and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting. Results: Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH) expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage. Conclusion: Chronic administration of fatty acid amide hydrolase (FAAH) inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension

Polak

Harasim-Symbor

Malinowska

et al. 2018

Cell Physiol Biochem

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“…Therefore, in various forms of hypertension, the eCB system becomes tonically active. This occurs by enhancing the vasorelaxant responses to eCBs, changes in plasma eCB concentration or alterations in the vascular expression of eCB system components, including up‐regulation of CB 1 receptors . It is worth mentioning that more research concerns the possible role of the eCB system in cardiovascular regulation in hypertension …”

Section: Introductionmentioning

confidence: 99%

“…This occurs by enhancing the vasorelaxant responses to eCBs, changes in plasma eCB concentration or alterations in the vascular expression of eCB system components, including up-regulation of CB 1 receptors. [3][4][5][6][7] It is worth mentioning that more research concerns the possible role of the eCB system in cardiovascular regulation in hypertension. [3,6,8] Cannabinoid signalling through the CB 1 -sensitive pathway can cause vasorelaxation via activation of nitric oxide synthase, increase in cyclic guanosine monophosphate and opening of potassium channels which causes membrane hyperpolarization, [5,9] see also Table 1.…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoids modulate Gq/11 protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism

Karpińska

Baranowska-Kuczko

Kloza

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Moreover, URB597 reduced cardiac and renal hypertrophy in younger and hypertrophy of aorta and coronary vessels (but not mesenteric artery) in older DOCA‐salt rats. However, it did not diminish organ hypertrophy in SHR as well as cardiomyocyte dimension and density of coronary blood vessels in DOCA‐salt animals (Toczek et al ., and unpublished; Polak et al ., ).…”

Section: Effects Of Chronic Cannabinoid Administration On Cardiovascumentioning

confidence: 97%

Cannabinoids in arterial, pulmonary and portal hypertension – mechanisms of action and potential therapeutic significance

Malinowska

Toczek

Pędzińska-Betiuk

et al. 2018

British J Pharmacology

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The endocannabinoid system is overactivated in arterial, pulmonary and portal hypertension. In this paper, we present limited clinical data concerning the role of cannabinoids in human hypertension including polymorphism of endocannabinoid system components. We underline differences between the acute cannabinoid administration and their potential hypotensive effect after chronic application in experimental hypertension. We discuss pleiotropic effects of cannabinoids on the cardiovascular system mediated via numerous neuronal and non‐neuronal mechanisms both in normotension and in hypertension. The final results are dependent on the model of hypertension, age, sex, the cannabinoid ligands used or the action via endocannabinoid metabolites. More experimental and clinical studies are needed to clarify the role of endocannabinoids in hypertension, not only in the search for new therapeutic strategies but also in the context of cardiovascular effects of cannabinoids and the steadily increasing legalization of cannabis use for recreational and medical purposes. Linked Articles This article is part of a themed section on 8 th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc

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Age-specific influences of chronic administration of the fatty acid amide hydrolase inhibitor URB597 on cardiovascular parameters and organ hypertrophy in DOCA-salt hypertensive rats

Cited by 29 publications

References 38 publications

The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension

The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension

Endocannabinoids modulate Gq/11 protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism

Cannabinoids in arterial, pulmonary and portal hypertension – mechanisms of action and potential therapeutic significance

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