Presynaptic cannabinoid CB<sub>1</sub> receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

Godlewski, Grzegorz; Malinowska, Barbara; Schlicker, Eberhard

doi:10.1038/sj.bjp.0705839

Cited by 33 publications

(26 citation statements)

References 35 publications

(45 reference statements)

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“…Interestingly, another recent study has demonstrated that the CB 1 -selective cannabinoid antagonist AM281 prevented the hemodynamic changes induced by acute LPS injection in rats (Kadoi et al, 2005a). Other results indicate that endocannabinoids may also contribute to endotoxin-induced hypotension indirectly, through CB 1 -mediated prejunctional inhibition of sympathoexcitation (Godlewski et al, 2004). In a different shock model in which continuous infusion of LPS in conscious rats causes marked peripheral vasodilatation and increased cardiac output, AM251 attenuated the tachycardic and hind quarter vasodilator effects of LPS.…”

Section: Cardiovascular and Respiratory Disordersmentioning

confidence: 94%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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Section: Cardiovascular and Respiratory Disordersmentioning

confidence: 94%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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“…This is an important point, because the hypotension after bolus administration of LPS is primarily due to a fall in cardiac output rather than to vasodilatation (11). Furthermore, more recently, Godlewski et al (19) indicated that in septic shock, endocannabinoids might exert an indirect action through prejunctional inhibition of sympathoexcitation.…”

Section: ) Receptor Antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-mentioning

confidence: 99%

Involvement of CB₁-receptors and β-adrenoceptors in the regional hemodynamic responses to lipopolysaccharide infusion in conscious rats

Gardiner¹,

March²,

Kemp³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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A possible involvement of endocannabinoids in a chronic model of endotoxemia was assessed by measuring the regional (renal, mesenteric, hindquarters) hemodynamic responses to continuous 24-h LPS infusion (150 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) in conscious, male Sprague-Dawley rats, in the absence or presence of the cannabinoid (CB 1) receptor antagonist AM-251 (3 mg/kg). AM-251 inhibited the tachycardic and hindquarters vasodilator effects of LPS, but did not influence the other hemodynamic changes. In subsequent experiments, it was shown that the tachycardic and hindquarters vasodilator effects of LPS were also inhibited by the nonselective ␤-adrenoceptor antagonist propranolol. In addition, the late (at 24 h) hindquarters vasodilator effects of LPS were inhibited by the ␤2-adrenoceptor antagonist ICI-118551. Against the background of our previous work showing ␤-adrenoceptor involvement in the cardiovascular effects of exogenous cannabinoids, we conclude that AM-251 may have been inhibiting endocannabinoid-modulated, sympathoadrenal-mediated activation of vasodilator ␤-adrenoceptors in LPS-infused rats rather than suppressing a direct vasodilator action of endocannabinoids.AM-251; endotoxemia; vasodilatation THE SYSTEMIC RESPONSE TO BACTERIAL infection, often referred to as sepsis, involves complex pathogenetic mechanisms and associated cardiovascular changes (26). Before the development of septic shock, there may be a hyperdynamic phase of sepsis with high cardiac output and peripheral vasodilatation (26). The underlying causes of the vasodilatation are multifactorial, involving the loss of vascular sensitivity to vasoconstrictors (25), some of which may be released through nonbaroreflex-mediated processes (39) and possibly contributed to by disorders of baroreflex control (29). In addition, there are numerous potential vasodilator mediators reported to be involved in the cardiovascular sequelae of sepsis (25).Endotoxemia induced by the administration of the bacterial cell wall product, LPS, to experimental animals is often used to model some of the pathophysiological changes occurring in sepsis. In a model of endotoxemia, involving a large bolus dose of LPS in anesthetized male Sprague-Dawley rats, Varga et al. -141716A) prevented the fall in mean arterial blood pressure. In addition, LPS stimulated the production of endocannabinoids by platelets and macrophages, although increased circulating levels of these substances were not directly demonstrated in LPS-treated rats (33). The same group has also shown an involvement of endogenous cannabinoids in the hypotension associated with hemorrhagic shock (35) and after myocardial infarction (34). In vitro studies (28) have shown cannabinoids cause vasodilatation by a variety of mechanisms, including release of endothelium-derived hyperpolarizing factor, activation of potassium channels, inhibition of calcium channels, direct effects of cannabinoid receptors on vascular smooth muscle, release of mediators from sensory nerves, and presynaptic inhibition of norepinephrine release. ...

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“…Several lines of evidence implicate the involvement of cannabinoids, acting via cannabinoid CB1 receptors, in the action of LPS in the rat (Varga et al, 1998). The systemic administration of a selective CB1 receptor antagonist SR141716 protects rats against hypotension induced by bacterial LPS (Varga et al, 1998), and in the initial phase of septic shock induced by LPS, the activation of CB1 receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic vasopressor response (Godlewski et al, 2004). CB1 receptors contribute to the immunosuppressive effects of HU210, both centrally and peripherally, since SR141716 attenuated, albeit partially, the decrease in LPS-induced cytokine release induced by this cannabinoid receptor agonist (Roche et al, 2006).…”

mentioning

confidence: 99%

A Novel Role of Cannabinoids: Implication in the Fever Induced by Bacterial Lipopolysaccharide

Benamar

Yondorf²,

Meissler³

et al. 2006

J Pharmacol Exp Ther

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There is continuing interest in elucidating the actions of drugs of abuse on the immune system and on infection. The present study investigated the effects of the cannabinoid (CB) receptor agonist aminoalkylindole, (ϩ)-WIN 55,212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], on fever produced after injection of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, the best known and most frequently used experimental model. Intraperitoneal injection of LPS (50 g/kg) induced a biphasic fever, with the first peak at 180 min and the second at 300 min postinjection.

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Presynaptic cannabinoid CB₁ receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

Cited by 33 publications

References 35 publications

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Involvement of CB₁-receptors and β-adrenoceptors in the regional hemodynamic responses to lipopolysaccharide infusion in conscious rats

A Novel Role of Cannabinoids: Implication in the Fever Induced by Bacterial Lipopolysaccharide

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Presynaptic cannabinoid CB1 receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

Cited by 33 publications

References 35 publications

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Involvement of CB1-receptors and β-adrenoceptors in the regional hemodynamic responses to lipopolysaccharide infusion in conscious rats

A Novel Role of Cannabinoids: Implication in the Fever Induced by Bacterial Lipopolysaccharide

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Presynaptic cannabinoid CB₁ receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

Involvement of CB₁-receptors and β-adrenoceptors in the regional hemodynamic responses to lipopolysaccharide infusion in conscious rats