Effects of aminoguanidine on endotoxin-induced pulmonary injury in rats

[ Abstract ] Objective To investigate the effects of inducible NO synthase (NOS) inhibitor aminoguanidine (AG) on endotoxin-induced pulmonary injury in rats. Methods Forty healthy male SD rats weighing 280-320 g were anesthetized with 20% urethane 1-1.2 g kg-1 ip. Right common carotid artery was cannulated for MAP monitoring and left jugular vein was cannulated for medication and blood sampling. The animals were randomly divided into five equal groups : group Ⅰ control; group Ⅱ lipopolysaccharide ( LPS 5 mg kg-1);group Ⅲ high-dose AG (100 mg-kg-1) sgroup IV medium-dose AG (50 mg kg-1) and group V low-dose AG (25 mg kg-1). In group Ⅱ - Ⅴ LPS was given iv 1 h after arterial and venous cannulation was completed. In group I normal saline was given iv instead of LPS. In group DI , IV and V AG was given ip 3 h after LPS. In group Ⅰ and Ⅱ normal saline was given instead of AG. Venous blood samples were taken 1, 3 and 6 h after LPS for determination of plasma NO concentration. The animals were then sacrificed and the lungs were immediately removed for determination of pulmonary coefficient ( lung weight/body weight) , lung water and MDA content, NOS and SOD activities and microscopic examination. Results (1) In LPS group MAP was decreasing after LPS administration. In group III and IV MAP increased significantly after AG administration. (2) In LPS group plasma NO concentration was increasing after LPS and was significantly higher than that in control group at 3 and 6 h after LPS (P 0.05). In group Ⅲ and IV ( high- and medium-dose AG) plasma NO concentration was significantly lower than that in LPS group at 6 h after LPS. (3) In group II NOS activity, MDA and water content in the lungs and pulmonary coefficient were significantly higher than those in control group ( P 0.01); lung SOD activity was significantly decreased. In group Ⅲ , Ⅳ and Ⅴ pulmonary coefficient, lung MDA content were significantly decreased as compared with those in LPS group (p 0.01 or0.05) and lung SOD activity was significantly increased. In group Ⅲ and W ( high- and medium-dose AG) lung water and NOS activity were significantly decreased. (4) The pathologic changes induced by LPS were significantly attenuated by AG. Conclusion AG is effective in attenuating the lung injury induced by LPS in a dose dependent manner.