Changes of Endothelin-1 and Nitric Oxide Systems in Brain Tissue During Mild Hypothermia in a Porcine Model of Cardiac Arrest

Background Our previous study found that mild hypothermia (MH) after resuscitation reduced cerebral microcirculation, but the mechanism was not elucidated. The aim of this study was to clarify changes of endothelin-1 (ET-1) and nitric oxide (NO) systems in brain tissue during hypothermia after resuscitation. Methods Twenty-six domestic male Beijing Landrace pigs were used in this study. MH was intravascularly induced 1 h after resuscitation from 8-min ventricular fibrillation. Core temperature was reduced to 33 °C and maintained until 8 h after resuscitation, and then animals were euthanized. ET-1 and NO levels in brain tissue and peripheral plasma were measured. Expression of endothelin-converting enzyme-1 (ECE-1), endothelin A receptor (ET-AR), endothelin-B receptor, and nitric oxide synthase (NOS) in brain tissue was determined by Western blot analysis. Results Compared with non-hypothermia (NH) treatment, MH after resuscitation significantly increased the level of endothelin-1 and reduced the level of NO in peripheral blood and brain tissue. Cerebral expression of ECE-1 and ET-AR was significantly increased during MH after resuscitation. Moreover, MH significantly decreased inducible NOS expression compared with the NH group. Conclusions The ET-1 system is activated, while inducible NOS is inhibited in brain tissue during MH after resuscitation.