Nitric oxide does not cause extravasation in endotoxemic rats.
BACKGROUND
Nitric oxide (NO) formed from inducible NO synthase (iNOS) is assumed to promote vascular permeability in sepsis and endotoxemia.


METHODS
Thirty-seven anesthetized rats were examined for the effects of endotoxin. After randomization, 17 animals had lipopolysaccharide (LPS) administered and 20 rats served as controls and were given the corresponding volume of saline. The observation period was 5 hours after administration of endotoxin. Mean arterial blood pressure, heart rate, and hematocrit were recorded in all animals, and transcapillary exchange of albumin, tissue water content, immunohistochemistry for nitric oxide synthase, and blood gases were investigated in subsets of animals.


RESULTS
When anesthetized rats were studied for 5 hours after endotoxin (LPS), the sequestration of albumin decreased in the intestine (double-isotope method) and there was no increased water content (freeze-drying technique) when the elevated tissue plasma volume of the LPS-treated rats was corrected for. Immunohistochemical methods showed a similar distribution and intensity of staining for endothelial NOS and neuronal NOS in LPS and control groups. In the lung of the LPS-treated rats, there was a significantly larger number of infiltrating, inflammatory cells staining for iNOS. There was no iNOS demonstrated in vascular structures or heart.


CONCLUSIONS
At 5 hours after LPS, there was no increased loss of water or albumin from the circulation. This challenges the notion that NO causes vascular damage in endotoxemia and extravasation as an obligatory sequela to endotoxemia.
Metcalf
Kerstin
K
Department of Medicine and Care, Division of Anaesthesiology and Clinical Research Center, University of Linköping, Linköping, Sweden. kerstin.metxalf@lio.se
Berg
Anna
A
Ericson
Ann-Charlott
AC
Lisander
Bjorn
B
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D045604:Extracellular Fluid / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010953:Plasma Volume; D051381:Rats; D011920:Rats, Inbred WF; D012016:Reference Values; D014882:Water-Electrolyte Balance
D000418:Albumins; D008070:Lipopolysaccharides; D009569:Nitric Oxide