Effects of aminoguanidine administration on vascular hyporeactivity in thoracic aorta from endotoxaemic rats.
Overproduction of nitric oxide has been implicated in the pathogenesis of the vascular hyporesponsiveness of endotoxic shock. In this study, we investigated the effects of aminoguanidine, an inducible nitric oxide synthase inhibitor, on the decreased vascular responsiveness 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 (Escherichia coli serotype 055:B5). The thoracic aortas were removed 18 h after lipopolysaccharide administration and suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Contractile responses to phenylephrine and potassium chloride, and relaxant responses to acetylcholine were reduced in endotoxaemic animals. Aminoguanidine was ineffective in improving the vascular hypocontractility at 25 and 75 mg kg(-1) doses; but at 50 mg kg(-1) dose, it restored the decreased contractile responses toward normal values. Diminished relaxant responses to acetylcholine were restored by aminoguanidine at all three different doses. There were no significant differences in sodium nitroprusside induced relaxant responses between all groups. Administration of aminoguanidine in control animals did not change vascular responses to any agent. These data suggest that aminoguanidine treatment improves the vascular hyporesponsiveness to contractile- and endothelium-dependent relaxant agents observed in endotoxic shock.
Erol
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Department of Pharmacology, Faculty of Medicine, Ege University, 35100, Izmir, Bornova, Turkey.
Koşay
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000109:Acetylcholine; C004479:pimagedine