Acute effects of sarpogrelate, a 5-HT2A receptor antagonist on cytokine production in endotoxin shock model of rats.

Abstract

Serotonin (5-HT)(2A) receptors are involved in cytokine production in infection or sepsis. Therefore, 5-HT(2A) receptor antagonist might be useful to treat sepsis. The present study investigates the effects of a 5-HT(2A) receptor antagonist, sarpogrelate on endotoxin shock. Catheters were inserted into the femoral artery and vein of Sprague-Dawley rats. First, sarpogrelate 0 (control), 3, or 10 mg/kg dissolved in 0.5 ml of distilled water has been given, followed by endotoxin 10 mg/kg in saline 0.5 ml 5 min later. Blood pressure, pulse rate and survival rate were monitored in 20 rats per dose. Blood gas and plasma cytokine concentrations were measured in 8 rats per dose. In four rats each of sarpogrelate 0, 3, or 10 mg/kg, and sham operation, the lung histology was examined. Zero, 15, and 12 rats survived for 8 h in the control, 3 mg/kg, and 10 mg/kg groups, respectively. The control group had the lowest blood pressure, pulse rate, pH and arterial oxygen tension, and the highest arterial carbon dioxide tension and plasma IL-1beta concentration. The increase of TNF-alpha was significantly lower in 3 mg/kg group than in the control group. Pathological changes of the lung were inhibited in 3 and 10 mg/kg groups. In conclusion, sarpogrelate might be effective to decrease production of pro-inflammatory cytokines, to keep hemodynamics, to inhibit lung damage, and to decrease mortality in endotoxin shock.