Aminoguanidine does not influence tissue extravasation of albumin in endotoxaemic rats.
BACKGROUND
It is generally maintained that protein and fluid are lost from the circulation under septic conditions. The role played by an increased production of nitric oxide, by the inducible nitric oxide synthase (iNOS), in this process is unclear.


METHODS
Chloralose anaesthetised male Wistar rats received E. coli lipopolysaccharide (LPS), 3 mg kg(-1) i.v., and were studied for 5 h. Mean arterial pressure (MAP) and heart rate (HR) were monitored and haematocrit (Hct) was determined intermittently. Tissue plasma volume and tissue clearances of radiolabelled albumin over the last 2 h of the experiment were determined by a double-isotope method. In 8 rats, 2 h after LPS, aminoguanidine, an iNOS selective blocker, was given i.v. at a dose of 5 mg kg(-1). This was followed by a continuous infusion for the duration of the experiment; altogether 20 mg kg(-1) was administered. In the control group (n=8), a corresponding volume of saline was infused.


RESULTS
Aminoguanidine did not significantly influence Hct, MAP and HR, as evidenced by inter-group comparisons (Mann-Whitney test). Tissue plasma clearances of albumin and tissue plasma volume were similar in both groups.


CONCLUSIONS
Aminoguanidine at 20 mg kg(-1) did not reverse the haemodynamic changes induced by LPS. Neither did the drug affect the tissue plasma clearance of albumin or the tissue plasma volume.
Metcalf
K
K
Department of Anaesthesiology and Intensive Care and the Clinical Research Centre, University Hospital, Linköping, Sweden.
Lisander
B
B
D000418:Albumins / Q000378:metabolism*; D000465:Algorithms; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006146:Guanidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012711:Serum Albumin, Radio-Iodinated
D000418:Albumins; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D012711:Serum Albumin, Radio-Iodinated; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C004479:pimagedine