Albumin clearance in the endotoxemic rat after administration of N^ω-nitro-L-arginine methyl ester (L-name)

Introduction

Endotoxin (LPS) is a powerful activator of the inducible nitric oxide (NO) synthase. Whereas NO seems to be one factor behind the decreased responsiveness of the circulation to adrenergic stimulation in septic shock, the role of NO in increased vascular permeability is less clear. In a former study [1] we have shown that although NO production increased after LPS there was no increased extravasation of albumin in a wide variety of rat tissues examined; on the contrary clearance was decreased in the entire gastrointestinal tract. In this study tissue extravasation was examined after administration of the nitric oxide synthase inhibitor L-NAME.

Methods

Anaesthetised Wistar rats were given E. coli lipopolysaccharide (LPS) 3 mg/kg i.v. and were studied for 5 h. Mean arterial pressure (MAP) and heart rate (HR) were recorded. As an indicator of NO production methemoglobin (metHb) was measured in the beginning and end of experiments, 2 h after LPS a bolus of L-NAME 100 mg/kg, or saline, was given i.v. The tissue clearance of albumin was studied over the last 2 h of the experiment by means of a double isotope method [2].

Results

In response to LPS all rats had a drop in MAP. After administration of L-NAME (n = 7) MAP increased significantly as compared to controls (n = 8). MetHb increased during experiments in controls but not in NAME-treated rats. Tissue plasma clearance for albumin increased in the NAME-group in skin, skeletal muscle and heart and decreased in testes as compared to controls.

Discussion

We have shown an increased production of NO after LPS and the dose of L-NAME administered abolished this. No differences in gastrointestinal albumin clearance were detected between groups, however in heart, skeletal muscle and skin albumin extravasation was increased. We conclude that this is most likely due to changes in regional hemodynamics with locally increased capillary pressures leading to increased albumin filtration in certain tissues only. In the majority of tissues no differences were found.