Endocannabinoids as cardiovascular modulators

Kunos, George; Járai, Zoltán; Bátkai, Sándor; Goparaju, Sravan K.; Ishac, Edward J. N.; Liu, Jie; Wang, Lei; Wagner, Jens A.

doi:10.1016/s0009-3084(00)00194-8

Cited by 135 publications

(105 citation statements)

References 67 publications

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“…Thus, the initial, marked, but short-lived bradycardic response, which we observed at the highest dose of anandamide, has been reported by others in conscious and anaesthetized rats (Varga et al, 1995;Stein et al, 1996;Lake et al, 1997). Lake et al (1997) found, as we did, that the bradycardia was unaected by cannabinoid receptor antagonism, and Varga et al (1995) showed it was sensitive to atropine. Because of the extent and rapidity of the initial bradycardia, the accompanying cardiovascular changes were dicult to assess.…”

Section: Discussionsupporting

confidence: 89%

“…Others have shown, in anaesthetized rats, that there is a transient pressor response which is not sympathetically-mediated, and does not involve cannabinoid receptors (Lake et al, 1997). We tested the hypothesis that at least some component of the haemodynamic response to anandamide might involve 5-HT 3 -receptors, since we saw certain similarities between the eects of anandamide and aspects of the Bezold ± Jarisch re¯ex, and it has been reported that the latter is 5-HT 3 -receptor-mediated (Veelken et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…This optimism has probably been bolstered by observations indicating that endocannabinoids, such as anandamide, exert hypotensive eects (Varga et al, 1995;Lake et al, 1997) through peripheral actions which, largely, have been assumed to involve vasodilatation (see Hillard, 2000;Kunos et al, 2000, for reviews).…”

Section: Introductionmentioning

confidence: 99%

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Complex regional haemodynamic effects of anandamide in conscious rats

Gardiner

March

Kemp

et al. 2002

British J Pharmacology

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1 Experiments were carried out in conscious, chronically instrumented, male, Sprague-Dawley rats to delineate the regional haemodynamic eects of the putative endogenous cannabinoid, anandamide, (0.075 ± 3 mg kg 71 ), and to dissect some of the mechanisms involved. 2 At all doses of anandamide, there was a signi®cant, short-lived increase in mean arterial blood pressure associated with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3 The higher doses (2.5 and 3 mg kg 71 ), caused an initial, marked bradycardia accompanied, in some animals, by a fall in arterial blood pressure which preceded the hypertension. In addition, after the higher doses of anandamide, the hindquarters vasoconstriction was followed by vasodilatation. 4 Although some of the eects described above resembled those of 5-HT (25 mg kg 71 ), the bradycardia and hypotensive actions of the latter were abolished by the 5HT 3 -receptor antagonist, azasetron, whereas those of anandamide were generally unaected. 5 None of the cardiovascular actions of anandamide were in¯uenced by the CB 1 -receptor antagonist, AM 251, but its bradycardic eect was sensitive to atropine, and its hindquarters vasodilator action was suppressed by the b 2 -adrenoceptor antagonist, ICI 118551. 6 The results dier, in several aspects, from those previously reported in anaesthetized animals, and underscore the important impact anaesthesia can have on responses to anandamide.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Complex regional haemodynamic effects of anandamide in conscious rats

Gardiner

March

Kemp

et al. 2002

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%

The complexities of the cardiovascular actions of cannabinoids

Randall

Kendall

O’Sullivan

2004

British J Pharmacology

141

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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“…To date, two such receptors have been identified: the CB 1 receptor, which is highly expressed in the brain (Matsuda et al, 1990), but is also present in heart and vascular tissues (Gebremedhin et al, 1999;Liu et al, 2000;Bonz et al, 2003), and the CB 2 receptor, expressed primarily by haematopoietic and immune cells (Munro et al, 1993). 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).…”

Section: Introductionmentioning

confidence: 99%

Blood pressure regulation by endocannabinoids and their receptors

2005

Self Cite

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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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Endocannabinoids as cardiovascular modulators

Cited by 135 publications

References 67 publications

Complex regional haemodynamic effects of anandamide in conscious rats

Complex regional haemodynamic effects of anandamide in conscious rats

The complexities of the cardiovascular actions of cannabinoids

Blood pressure regulation by endocannabinoids and their receptors

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