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The viscosity of the extracellular medium of cultured hepatocytes has been shown to be a regulator of the secretion and synthesis of very low-density lipoproteins (Yedgar et al., J. Biol. Chem. 257: 2188-2192, 1982). At present, the role of plasma viscosity in regulation of plasma lipoprotein levels was examined in vivo using nephrotic hyperlipidemic rats. Plasma viscosity was increased by injection of macromolecules: simultaneously with induction of nephrosis by aminonucleoside; and after the lipid level had reached its maximum. In experiment 1 the elevation of plasma viscosity (which persisted for at least 2 days) delayed the development of the hyperlipidemia by at least 2 days. In experiment 2 increasing the plasma viscosity reduced plasma triglyceride and cholesterol levels by 70 and 40%, respectively, within 2 days. The hyperlipidemia was accompanied by increased plasma viscosity. The contribution of lipoproteins to plasma viscosity was 27% in the nephrotic-hyperlipidemic rats, compared with 4% in normal rats. It is suggested that plasma viscosity regulates lipoprotein levels in vivo concordant with the observation in cultured hepatocytes.
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