Endogenous nitric oxide in the maintenance of rat microvascular integrity against widespread plasma leakage following abdominal laparotomy

1 The role of nitric oxide (NO) in the maintenance of microvascular integri ty during minor surgical manipulation has been evaluated in the rat. 2 The NO synthase inhibitors, N-G-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1), s.c.) and N-G-monomethyl-L-arginine (L-NMMA, 50 mg kg(-1), s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h i n the stomach, duodenum, jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone-anaesthetized rat. 3 In contrast, in anaesthetized rats with a midline abdominal laparotomy (5 cm), L-NAME (1 - 5 mg kg(-1), s.c.) or L-NMMA (12.5 - 50 mg kg(-1), s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular l eakage, effects reversed by L-arginine pretreatment (300 mg kg(-1), s.c., 1 5 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 4 Pretreatment with a rabbit anti-rat neutrophil serum (0.4 ml kg(-1), i.p. ), 4 h before laparotomy, abolished the plasma leakage induced by L-NAME in all the organs investigated. 5 These results indicate that the following abdominal laparotomy, inhibitio n of constitutive NO synthase provokes vascular leakage in the general micr ocirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibito rs using acute surgically prepared in vivo models. The findings thus sugges t that constitutively-formed NO has a crucial role in the maintenance of ac ute microvascular integrity following abdominal surgical intervention.