Rimonabant, a specific antagonist of the cannabinoid CB1-receptor, prevents lipopolysaccharide-induced endotoxemia in awake guinea pigs

Abstract

2-arachidonoyl glycerol (2-AG), an endogenous cannabinoid, has been drawing much attention as an early stage mediator at the onset of sepsis. In the present study, we investigated weather rimonabant, one of the CB1 antagonists, alleviated the medical conditions during endotoxemia and measured the level of prostaglandin E metabolite (PGEM). A cylindrical electric transmitter was connected to the transducer via a cable embedded beneath the animal's dorsal skin and sutured in place. Signals from the transmitter were detected by a receiver placed directly beneath the cage via telemetry. We monitored arterial pressure via catheter in the carotid artery and administrated drugs via catheter in jugular vein. We separated animals into three groups. The control group received lipopolysaccharide (LPS, 0.3 mg/kg, i.v.) and vehicle i.v. Experimental animals received LPS and rimonabant (1, 3 mg/kg/h) i.v. Ten minutes after the injection of the vehicle or rimonabant, LPS (0.3 mg/kg, i.v.) was administered. The prostaglandin E metabolites (PGEM) levels were measured by EIASA. In the control group, LPS induced intestinal paralysis and the decline in blood pressure peaked 1-3h after administration of LPS. In rimonabant-treated group, rimonabant inhibited LPS-induced intestinal paralysis and hypotension. Levels of PGEM in guinea pig was increased by LPS-administrate, rimonabant inhibits PGEM increase. The results suggest that rimonabant was effective against LPS-induced endotoxemia in guinea pigs. (JJAAM. 2010; 21: 118-25)

Effects of simultaneous treatment with PMX-DHP and sivelestat on endotoxaemia in conscious guinea pigs

“…PMX treatment removes LPS and LPS-induced endocannabinoids 5,12) . Endocannabinoids, particularly 2-arachidonylglycerol (2-AG), are attracting attention as early initial mediators of sepsis 17,18) . PMX treatment is effective because it is etiotropic.…”