REDUCED PRESSOR ACTIVITY OF MIDAGLIZOLE (SELECTIVE ALPHA(2)-ADRENERGIC ANTAGONIST) IN HEMORRHAGIC RATS

Midaglizole (DG5128) is a selective alpha(2)-adrenergic antagonist. Ho wever, the hemodynamic effect in hemorrhage remains unclear. The prese nt study examines the effects of 10 mg.kg(-1) midaglizole on mean arte rial pressure (MAP) changes following hemorrhagic shock in rats. Hemor rhagic shock was induced by withdrawing blood from the right carotid a rtery and MAP was maintained at 40 mmHg until 40% of the withdrawn blo od had been reinfused. The remaining blood was then slowly infused int o the rat. The rats received 10 mg.kg(-1) midaglizole (n = 8) or salin e (n = 6) 20 min after reinfusion. Sham-shock rats were observed for 9 0 min without performing the hemorrhage shock protocol and then admini stered 10 mg.kg(-1) midaglizole (n = 11). In sham-shock rats, MAP incr eased maximally 24 s after midaglizole administration, whereas MAP dec reased significantly 36-60 s after midaglizole administration in hemor rhagic rats. This difference may result from blockage of peripheral po st-synaptic alpha(2)-adrenoceptors. Thus, vasoconstriction due to post -synaptic alpha(2)-adrenoceptor activation may play a more important r ole 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.