Reduced pressor activity of midaglizole (selective alpha2-adrenergic antagonist) in hemorrhagic rats

Midaglizole (DG5128) is a selective alpha2-adrenergic antagonist. However, the hemodynamic effect in hemorrhage remains unclear. The present study examines the effects of 10 mg x kg(-1) midaglizole on mean arterial pressure (MAP) changes following hemorrhagic shock in rats. Hemorrhagic shock was induced by withdrawing blood from the right carotid artery and MAP was maintained at 40 mmHg until 40% of the withdrawn blood had been reinfused. The remaining blood was then slowly infused into the rat. The rats received 10 mg x kg(-1) midaglizole (n = 8) or saline (n = 6) 20 min after reinfusion. Sham-shock rats were observed for 90 min without performing the hemorrhage shock protocol and then administered 10 mg x kg(-1) midaglizole (n = 11). In sham-shock rats, MAP increased maximally 24 s after midaglizole administration, whereas MAP decreased significantly 36-60 s after midaglizole administration in hemorrhagic rats. This difference may result from blockage of peripheral post-synaptic alpha2-adrenoceptors. Thus, vasoconstriction due to post-synaptic alpha2-adrenoceptor activation may play a more important role in maintaining blood pressure during hemorrhagic shock than under normal conditions. Based on the present results, caution is warranted when administering midaglizole in hemorrhagic hypotension.