Role of ET and NO in resuscitative effect of diaspirin cross-linked hemoglobin after hemorrhage in rat

被引:70
作者
Gulati, A
Sen, AP
Sharma, AC
Singh, G
机构
[1] Univ Illinois, Dept Pharmaceut & Phamacodynam, Hlth Sci Ctr, Chicago, IL 60612 USA
[2] Univ Illinois, Hlth Sci Ctr, Dept Rehabil Med, Chicago, IL 60612 USA
[3] Univ Illinois, Hlth Sci Ctr, Dept Restorat Med Sci, Chicago, IL 60612 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1997年 / 273卷 / 02期
关键词
hemoglobin-based therapeutic agent; endothelin; regional blood flow; nitric oxide; N-G-nitro-L-arginine methyl ester; FR-139317; guanosine; 3; 5 '-cyclic monophosphate; hemorrhagic shock;
D O I
10.1152/ajpheart.1997.273.2.H827
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based therapeutic agent that produces significant cardiovascular effects, possibly due to its actions on vasoactive substances, such as endothelin (ET) and nitric oxide (NO). We have studied the modulation of cardiovascular effects of DCLHb by an NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), and an ETA-receptor antagonist, FR-139317, in hemorrhaged rats. Control rats resuscitated with vehicle [Ringer lactate (RL), 4 ml/kg iv] did not show any improvement in O-2 consumption, base deficit, systemic hemodynamics, or regional blood flow after hemorrhage, and the rats survived for <70 min. Administration of DCLHb (400 mg/kg iv) significantly improved O-2 consumption, base deficit, systemic hemodynamics, and regional blood circulation after resuscitation, and the rats survived for >120 min after hemorrhage. Plasma ET-1 and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations increased after hemorrhage. DCLHb produced an increase in ET-1 and decreased cGMP concentrations in plasma. Pretreatment with L-NAME (10 mg/kg iv) or FR-139317 (4 mg/kg iv) attenuated the DCLHb-induced improvement in survival time, base deficit, systemic hemodynamics, and regional blood circulation. L-NAME (10 mg/kg iv) per se did not produce any resuscitative effect; therefore the NO mechanism may not be contributing toward the efficacy of DCLHb in hemorrhaged rats. However, FR-139317 attenuated the efficacy of DCLHb; therefore an increase in plasma ET-1 concentration by DCLHb may be contributing toward the efficacy of DCLHb in hemorrhage. Hemorrhage-induced increase in cGMP levels could be attenuated by L-NAME, but L-NAME was not effective in resuscitation of hemorrhaged rats, indicating a lack of role of NO in resuscitation. It is concluded that the ET mechanism is more important in the beneficial effect of DCLHb than the NO mechanism in hemorrhage.
引用
收藏
页码:H827 / H836
页数:10
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