Altered renal cortical reabsorption of protein and urinary excretion of sodium in relation to vascular leakage induced by horseradish peroxidase

Abstract

The intravenous injection of horseradish peroxidase (HRP) into rats of the Sprague-Dawley strain caused vascular leakage as detectable by a 20-40% increase in the hematocrit and a 15-20% decrease in plasma protein concentration. These changes did not occur when the same amounts of HRP were injected into rats pretreated with antagonists to histamine and serotonin. After pretreatment with the antagonists, the reabsorption of HRP by the proximal tubule cells (the concentration of HRP in the total particulate fractions) showed a 77% decrease and the urinary excretion of sodium showed more than an 80% increase as compared to the values from rats treated with HRP alone. In addition, the blood clearance rate of HRP was decreased and the urinary excretion of HRP was increased after treatment with the antagonists to histamine and serotonin. Cytochemical observations of formaldehyde vapor-fixed tissue also showed the effects of vascular leakage. After the injection of HRP in physiologic or hypertonic saline, the basal infoldings of the proximal tubule cells were strongly peroxidase-positive. When the same amounts of HRP were injected after pretreatment with antagonists to histamine and serotonin, or with mannitol, the basal infoldings were not stained or were stained faintly. Rats of the Wistar/Furth strain did not show the effects of vascular leakage observed with rats of the Sprague-Dawley strains. The questions are discussed as to whether the marked depression of renal cortical HRP absorption by mannitol and hypertonic saline (J Histochem Cytochem 23:707, 1975) is related to the prevention of vascular leakage, and whether the reabsorption of both sodium and protein is increased during the leakage of serum proteins into the interstitial tissue.