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

Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Medical School, Queen's Medical Centre, Nottingham, United Kingdom

Submitted 8 August 2004 ; accepted in final form 24 December 2004

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 µg·kg^–1·h^–1) in conscious, male Sprague-Dawley rats, in the absence or presence of the cannabinoid (CB₁) 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

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