Cardiovascular effects of cannabinoids

Randall, Michael D.; Harris, David W.; Kendall, David A.; Ralevic, Vera

doi:10.1016/s0163-7258(02)00258-9

Cited by 118 publications

(116 citation statements)

References 73 publications

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“…There are different mechanisms of CB-mediated vasorelaxation depending on the vascular bed studied (see Randall et al, 2002). For example, vasorelaxation to anandamide in the rat coronary vessels does not involve sensory nerves (White et al, 2001), and Andersson et al (2002) showed that, while anandamide is a full agonist of the VR in guinea-pig mesenteric arteries, it is a weak agonist of this receptor in main bronchi.…”

Section: Se O'sullivan Et Al Vasorelaxant Effects Of Nada 809mentioning

confidence: 99%

“…To date, the cardiovascular actions of NADA have not been examined; however, the effects of the prototypic endocannabinoid anandamide have been widely studied (for a review, see Randall et al, 2002). Several putative mechanisms have been put forward to explain the vasorelaxant effects of anandamide; however, many discrepancies still occur in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of the vasorelaxant properties of the novel endocannabinoid N‐arachidonoyl‐dopamine (NADA)

O’Sullivan

Kendall

Randall

2004

British J Pharmacology

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1 We have investigated the vascular effects of N-arachidonoyl-dopamine (NADA), a novel endocannabinoid/vanilloid. NADA caused vasorelaxant effects comparable to those of anandamide in small mesenteric vessels (G3), the superior mesenteric artery (G0) and in the aorta. 2 In G3, addition of N G -nitro-L-arginine methyl ester (300 mM) or the dopamine (D 1 ) receptor antagonist (SCH23390, 1 mM) did not affect responses to NADA. In the presence of 60 mM KCl, after de-endothelialisation, or after K þ channel inhibition with charybdotoxin (100 nM) and apamin (500 nM), relaxant responses to NADA were inhibited. 3 In G3, pretreatment with the vanilloid receptor (VR) agonist capsaicin (10 mM) or the VR antagonist capsazepine (10 mM) reduced vasorelaxation to NADA. 4 In G3, application of the CB 1 antagonist SR141716A at 1 mM but not 100 nM reduced the potency of NADA. Another CB 1 antagonist, AM251 (100 nM and 1 mM), did not affect vasorelaxation to NADA. After endothelial denudation, SR141716A (1 mM) did not reduce the responses further. A combination of capsaicin and SR141716A (1 mM) reduced vasorelaxation to NADA further than with capsaicin pretreatment alone. The novel endothelial cannabinoid (CB) receptor antagonist O-1918 opposed vasorelaxation to NADA in G3. 5 In the superior mesenteric artery (G0), vasorelaxation to NADA was not dependent on an intact endothelium and was not sensitive to O-1918, but was sensitive to capsaicin and SR141716A or AM251 (both 100 nM). 6 The results of the present study demonstrate for the first time that NADA is a potent vasorelaxant. In G3, the effects of NADA are mediated by stimulation of the VR and the novel endothelial CB receptor, while in G0, vasorelaxation is mediated through VR 1 and CB 1 receptors.

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Section: Se O'sullivan Et Al Vasorelaxant Effects Of Nada 809mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterisation of the vasorelaxant properties of the novel endocannabinoid N‐arachidonoyl‐dopamine (NADA)

O’Sullivan

Kendall

Randall

2004

British J Pharmacology

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“…The cardiovascular effects of both synthetic and endogenous cannabinoids have been extensively examined and reviewed (see Hillard, 2000;Kunos et al, 2000;Ralevic et al, 2002;Randall et al, 2002). What is clear is that the cardiovascular actions of the cannabinoids are complex and appear to be complicated by differences in experimental approach and prevailing conditions.…”

Section: Introductionmentioning

confidence: 99%

“…A more detailed overview of in vitro effects of anandamide can be found in the following reviews Ho¨gestatt & Zygmunt, 2002;Randall et al, 2002). Some studies have implicated the endothelium in relaxant responses to anandamide (Pratt et al, 1998;Chaytor et al, 1999;Wagner et al, 1999), with the release of prostanoids (Ellis et al, 1995;Fleming et al, 1999), nitric oxide (Deutsch et al, 1997) or endothelial-derived hyperpolarising factor (EDHF) (Chaytor et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The complexities of the cardiovascular actions of cannabinoids

Randall

Kendall

O’Sullivan

2004

British J Pharmacology

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142

122

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The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long-lasting hypotension. However, in conscious animals, the picture is one of bradycardia followed by pressor responses. Clearly, the responses to cannabinoids are dependent on the experimental conditions and synthetic cannabinoids and endocannabinoids exhibit different pharmacologies. In terms of mechanisms involved in the vascular responses to cannabinoids, the following have been implicated: the involvement of 'classical' cannabinoid receptors, the involvement of a novel endothelial cannabinoid receptor, the release of nitric oxide, the release of endotheliumderived hyperpolarising factor (EDHF), the activation of vanilloid receptors, metabolism of endocannabinoids to vasoactive molecules, and both peripheral inhibition and central excitation of the sympathetic nervous system.

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“…Arachidonoyl ethanolamide or anandamide and 2-arachidonoylglycerol, the natural ligands of these receptors, are lipid-like substances called endocannabinoids (reviewed by Mechoulam et al, 1998;Kunos et al, 2000). Apart from their well-known neurobehavioral and immunological actions, cannabinoids also elicit potent cardiovascular effects, such as profound hypotension (Lake et al, 1997a;Hillard, 2000;Kunos et al, 2002;Randall et al, 2002;Ralevic et al, 2002). Although several lines of evidence indicate that the cardiovascular depressive effects of cannabinoids are mediated by peripherally localized CB 1 receptors, recent studies also suggest the existence of as yet undefined endothelial and cardiac receptor(s) that mediate certain endocannabinoid-induced cardiovascular effects Járai et al, 1999;Ford et al, 2002;Ho and Hiley, 2003;Kunos et al, 2002;Offertáler et al, 2003;O'Sullivan et al, 2004), however, the discussion of the latter is beyond the main scope of this summary.…”

Section: Introductionmentioning

confidence: 99%

Blood pressure regulation by endocannabinoids and their receptors

2005

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Cannabinoids and their endogenous and synthetic analogs exert powerful hypotensive and cardiodepressor effects by complex mechanisms involving direct and indirect effects on myocardium and vasculature. On the one hand, endocannabinoids and cannabinoid receptors have been implicated in the hypotensive state associated with hemorrhagic, endotoxic and cardiogenic shock, and advanced liver cirrhosis. On the other hand, there is emerging evidence suggesting that the endocannabinergic system plays an important role in the cardiovascular regulation in hypertension. This review is aimed to discuss the in vivo hypotensive and cardiodepressant effects of cannabinoids mediated by cannabinoid and TRPV 1 receptors, and focuses on the novel therapeutical strategies offered by targeting the endocannabinoid system in the treatment of hypertension.

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Cardiovascular effects of cannabinoids

Cited by 118 publications

References 73 publications

Characterisation of the vasorelaxant properties of the novel endocannabinoid N‐arachidonoyl‐dopamine (NADA)

Characterisation of the vasorelaxant properties of the novel endocannabinoid N‐arachidonoyl‐dopamine (NADA)

The complexities of the cardiovascular actions of cannabinoids

Blood pressure regulation by endocannabinoids and their receptors

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