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In previous studies, bosentan was found to decrease plasma leptin concentrations after myocardial infarction (MI) in rats and had decreased mortality. The present study was undertaken to examine the effect of bosentan on leptin and endothelin-1 (ET-1) concentrations in plasma and ET-1 concentrations in the hippocampus after cardiac arrest (CA) in rats. Studies were performed in 72 rats divided into treated and untreated animals in the following experimental groups: control, 3 min, 10 min, 1 h, 24 h, and 7 days after CA. Bosentan was given daily 2 h before CA or decapitation, 7 days, by gavage at a dose of 100 mg/kg. Plasma leptin concentration decreased in the early period after CA, and being elevated in 24 h, normalized 1 week later. Bosentan kept plasma leptin concentration at the control level in the postischemic period. Plasma ET-1 concentration significantly increased during the postischemic period. Bosentan produced the elevation of plasma ET-1 concentration in the preischemic period and kept the level of ET-1 at control values after CA. Concentration of ET-1 in the hippocampus was significantly lower 24 h after CA and was elevated after 1 week. The most dramatic effect of bosentan on ET-1 concentration was in the hippocampus, where it significantly decreased during the entire postischemic recovery period. We postulate an important effect of bosentan on concentration of ET-1 and leptin in plasma and ET-1 in the brain after global cerebral ischemia caused by CA. Drug Dev Res 64:137-144, 2005.

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