INTRAVENOUS ENDOTOXIN DOES NOT INCREASE TISSUE EXTRAVASATION OF ALBUMIN IN RATS

Background: It is unclear whether activation of the inducible nitric o xide synthase (iNOS) increases or decreases the extravasation of plasm a. Methods: Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg-l i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pr essure (MAP) and heart rate (HR) were recorded. Tissue clearance of ra dio-labelled albumin, during the last 2 h of each experiment, was dete rmined by a double-isotope method. In separate animals, the serum conc entration of nitrite and nitrate was determined, 5 h after LPS or the solvent. Main Results: LPS initially decreased MAP and lastingly incre ased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was low er in the heart and calf muscle and increased only in diaphragm, compa red to corresponding control animals (n=8). Ln the 5-h LPS rats, clear ance was lowered (n=8) in the entire gastrointestinal tract and in tes tes, compared to controls (n=8). The serum nitrite/nitrate concentrati on was higher in animals given LPS (n=6) than in controls (n=6). Concl usion: After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is n ot necessarily associated with increased albumin extravasation.