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

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Abstract
The role of nitric oxide (NO) in the maintenance of microvascular integrity during minor surgical manipulation has been evaluated in the rat. The NO synthase inhibitors, NG‐nitro‐L‐arginine methyl ester (L‐NAME, 5 mg kg−1, s.c.) and NG‐monomethyl‐L‐arginine (L‐NMMA, 50 mg kg−1, s.c.) had no effect on microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum, jejunum, colon, lung and kidney in the un‐operated conscious or pentobarbitone‐anaesthetized rat. 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 leakage, effects reversed by L‐arginine pretreatment (300 mg kg−1, s.c., 15 min). These actions were not observed in anaesthetized rats that had only received a midline abdominal skin incision (5 cm). 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. These results indicate that the following abdominal laparotomy, inhibition of constitutive NO synthase provokes vascular leakage in the general microcirculation, by a process that may involve neutrophils. Such effects could thus confound studies on the microvascular actions of NO synthase inhibitors using acute surgically prepared in vivo models. The findings thus suggest that constitutively‐formed NO has a crucial role in the maintenance of acute microvascular integrity following abdominal surgical intervention. British Journal of Pharmacology (1999) 126, 515–521; doi:10.1038/sj.bjp.0702322