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.
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D044482:Benzeneacetamides; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D003106:Colon / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007553:Isotope Labeling; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D044482:Benzeneacetamides; D004731:Endotoxins; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D012709:Serum Albumin; C056616:N-(4-benzyloxybenzyl)acetohydroxamic acid; D009569:Nitric Oxide; D001120:Arginine; D001094:Arachidonate 5-Lipoxygenase; D019331:NG-Nitroarginine Methyl Ester