Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients

Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients. To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis

Difference of Lectin Receptors Between the Free Cell Type and Island Forming Cell Type of Rat Ascites Hepatoma Cells

The cell surface glycoconjugates of various rat ascites hepatoma cell lines with different degrees of adhesiveness were compared, by binding assays, using ^<125>I-labelled lectins. Effects of neuraminidase, TPCK-trypsin and chondroitinase ABC treatment of the cells, on the number of lectin receptor sites were also studied. The TPCK-trypsin treatment caused a marked decrease in the number of peanut agglutinin receptor sites on the island forming and mixed cell types. The decrease of wheat germ agglutinin receptor sites and the increase of castor bean agglutinin receptor sites, after neuraminidase treatment, were larger on the free cell type. It is therefore possible that α-sialyl-β-D-galactosyl residues are abundant on the cell surface of this type, and that its low cell adhesiveness may be due to a electrostatic repulsion of negative charges of the sialic acid