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

Abstract

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 microg.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 beta-adrenoceptor antagonist propranolol. In addition, the late (at 24 h) hindquarters vasodilator effects of LPS were inhibited by the beta2-adrenoceptor antagonist ICI-118551. Against the background of our previous work showing beta-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 beta-adrenoceptors in LPS-infused rats rather than suppressing a direct vasodilator action of endocannabinoids.