Effects of aminoguanidine administration on vascular hyporeactivity in thoracic aorta from endotoxaemic rats

Overproduction of nitric oxide has been implicated in the pathogenesis of t he vascular hyporesponsiveness of endotoxic shock. In this study, we invest igated the effects of aminoguanidine, an inducible nitric oxide synthase in hibitor, on the decreased vascular responsive ness in endotoxic shock. Male albino rats were administered intraperitoneally aminoguanidine (25, 50 or 75 mg kg(-1)) 1 h after they received saline or lipolysaccharide (Escherich ia coli serotype 055:B5). The thoracic aortas were removed 18 h after Lipop olysaccharide administration and suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Contractile responses to phen ylephrine and potassium chloride, and relaxant responses to acetylcholine w ere reduced in endotoxaemic animals. Aminoguanidine was ineffective in impr oving the vascular hypocontractility at 25 and 75 mg kg(-1) doses; but at 5 0 mg kg(-1) dose, it restored the decreased contractile responses toward no rmal values. Diminished relaxant responses to acetylcholine were restored b y aminoguanidine at all three different doses. There were no significant di fferences in sodium nitroprusside induced relaxant responses between all gr oups. Administration of aminoguanidine in control animals did not change va scular responses to any agent. These data suggest that aminoguanidine treat ment improves the vascular hyporesponsiveness to contractile- and endotheli um-dependent relaxant agents observed in endotoxic shock. (C) 2000 Elsevier Science B.V. All rights reserved.