Colonic Microvascular Integrity in Acute Endotoxaemia: Interactions Between Constitutive Nitric Oxide and 5-lipoxygenase Products

Administration of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (5 mg/kg s.c.) provoked acute microvascular injury (assessed by the leakage of radiolabelled human serum albumin) in the rat colon within 1 h, when administered concurrently with endotoxin (Escherichia coli lipopolysaccharide, 3 mg/kg i.v.). Pretreatment with the selective inhibitor of 5-lipoxygenase, BW A137C (N-[4-benzyloxybenzyl] acetohydroxamic acid; 1-20 mg/kg s.c., 15 min before endotoxin) attenuated such damage in a dose-dependent manner. These findings suggest a balance between protective constitutive nitric oxide and the detrimental actions of 5-lipoxygenase products in the maintenance of vascular integrity in the early stage of sepsis.