Nitric oxide hemoglobin in mice and rats in endotoxic shock.
Mice given ip bacterial endotoxin (LPS) at 10 mg/kg showed a statistically significant decrease in plasma glucose and an increase in hematocrit at 2 h after injection. Glucose was still decreased at 4 h, but the hematocrit had returned to control values. Nitrosylated hemoglobin (HbNO) was detected at 3, but not at 2 h. By 4 h it had increased 5-fold. When N-monomethylarginine (NMMA) at 100 mg/kg, ip was given 2 h after LPS in mice, the HbNO concentration at 4 h was significantly reduced, but the hypoglycemia was worsened because NMMA itself produced a significant hypoglycemia. Rats given iv LPS, 20 mg/kg, showed a fleeting, transient rise in mean arterial pressure (MAP) lasting only a few min. Thereafter, the MAP tended to drift slowly downward over 4 h, but when the MAP at 30 min intervals was compared to the pre-LPS MAP, there were no significant differences. Plasma glucose in unanesthetized rats was significantly elevated at 1 h, back to control at 2 h, and significantly decreased at 3 h. HbNO was detected as early as 1 h after injection. By 2 h the HbNO concentrations exceeded the highest levels found in mice, and they were still increasing as late as 5 h after injection. Unanesthetized rats showed toxic signs and 3/12 rats died within 4 hours of LPS administration. These results are consistent with a model for endotoxic shock in which LPS stimulates an inducible pathway for NO synthesis.
Wang
Q Z
QZ
Department of Pharmacology and Toxicology, Dartmouth College, Hanover, NH.
Jacobs
J
J
DeLeo
J
J
Kruszyna
H
H
Kruszyna
R
R
Smith
R
R
Wilcox
D
D
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000737:chemistry; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000097:blood*
D001786:Blood Glucose; D006454:Hemoglobins; D009569:Nitric Oxide