Effect of nitric oxide on mortality of mice after whole body hyperthermia.
The objective of this study is to find the role of nitric oxide (NO) in the haemodynamics of mice subjected to heat stress caused by Whole Body Hyperthermia (WBH) treatment. L-arginine (L-arg), a natural substrate for NO synthase (NOS), N-nitro-L-arginine methyl ester (L-NAME), a preferential inhibitor of endothelial NOS, and dexamethasone, a preferential inhibitor of inducible NOS, have been used to study the role of NO in thermal injury caused by WBH treatment. Nitrite in plasma and mortality of Swiss male mice subjected to WBH treatment induced by radiant heat (40 degrees C fo 1 h at 50-55% relative humidity), were monitored in mice pre-treated with either L-NAME, dexamethasone or L-arg. A batch of mice subjected to 24 h fasting prior to WBH treatment was also used to study the above parameters. Injections with 1.5 mg/kg or above of L-NAME just before WBH treatment, induced mortality in mice, with a corresponding drop in plasma nitrite values. L-arg (8 mg/kg) pre-treatment reversed the killing caused by L-NAME in WBH treated mice. L-arg (60 mg/kg) pre-treatment induced mortality in mice subjected to WBH treatment. In the fasted group, a very low dose of L-arg (8 mg/kg) given before WBH treatment led to a significant increase in plasma nitrite levels. In both the normal and fasted groups of mice, 120 mg/kg of L-arg pre-treatment resulted in a sharp increase in plasma nitrite values and subsequent death of mice. The results throw up an important finding, in that the interaction of elevated body temperature, with either a decrease or over production of nitrite oxide, leads to modulation of thermal injury of mice, caused by WBH treatment.
Poduval
T B
TB
Cell Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. tbpodu@magnum.barc.ernet.in
Chatterjee
S
S
Sainis
K B
KB
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000378:metabolism* / Q000401:mortality*; D005938:Glucocorticoids / Q000494:pharmacology; D006979:Hyperthermia, Induced / Q000401:mortality*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D015996:Survival Rate
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D009573:Nitrites; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester