Combined effects of dexamethasone and aminoguanidine on rats with endotoxemia.
The effects of a combination of dexamethasone (DEX, an inhibitor of inducible nitric oxide synthase (iNOS) synthesis) and aminoguanidine (AG, an inhibitor of iNOS activity) on the anesthetized rat treated with endotoxin (lipopolysaccharide, LPS) were examined. In addition, we investigated whether a complete inhibition of nitric oxide (NO) formation caused by LPS prevents the hypotension, restores the vascular hyporeactivity to normal and improves the survival rate. The combination of DEX (3 mg/kg at 30 min prior to LPS) plus AG (15 mg/kg at 2 h after LPS) inhibited the overproduction of nitrate (an indicator of NO) and prevented the development of delayed hypotension, but further enhanced tachycardia in rats treated with LPS for 6 h. In addition, the vascular hyporeactivity to norepinephrine (NE) was, however, only partially restored in endotoxemic rats treated with DEX plus AG. During the experimental period, the survival rate of LPS-rats treated with DEX plus AG was also improved when compared to that of rats treated with LPS only. The beneficial effects of the combined therapy with DEX plus AG on rats with endotoxemia, suggesting that (i) combined treatment of animals with DEX plus AG may reduce some of the detrimental effects of LPS and (ii) NO only partially contributes to the vascular hyporeactivity in endotoxic shock.
Wu
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CC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Yen
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MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004347:Drug Interactions; D019446:Endotoxemia / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006146:Guanidines / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D009638:Norepinephrine