Dual endothelin receptor antagonist reduces subcellular organelles damage in cerebral cortex neurons in experimental model of cardiac arrest

In the present study we investigated the effect of dual endothelin receptor (ETR) antagonist bosentan on postischemic structural abnormalities of subcellular organelles in neurons of cerebral cortex and on endothelin binding sites in the brain after 10 min of cardiac arrest in male Wistar rats. After seven days, cortical neurons in bosentantreated animals revealed diminished morphological changes compared with non-treated rats, including less advanced nuclear pore formation, disaggregation of ribosomes, abnormalities of Golgi network and better preservation of long neurotubules. The analysis of 125I-endothelin-1 binding in brain documented a decrease in endothelin-1 maximum density of receptors (Bmax) and equilibrium dissociation constant (KD) up to 1 week in untreated animals. In bosentan-treated animals above values increased postischemically. In conclusion, the results indicate that bosentan works towards salvage of cytoskeleton and other organelles of cortical neurons after cardiac arrest through a modulation of ETR signaling.