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Aminoguanidine does not influence tissue extravasation of albumin in endotoxaemic rats

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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. Conclusion:

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.

Keywords: Endotoxin; albumin; aminoguanidine; inducible nitric oxide synthase; nitric oxide; rats; tissue plasma clearance; vascular permeability

Document Type: Research Article

Publication date: January 1, 2001

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