EXPERIMENTAL AND MOLECULAR PATHOLOGY 57, 222-234 (1992) Microvascular Changes in Rat Glomeruli as a Consequence of Small Differences in Selenium Exposure C. D. ECKHERT,’ M. K. LOCKWOOD, M. H. Hsu, J. Ho, AND R. KANG Department of Environmental Health Sciences, University of California, Los Angeles, California 90024-1772 Received February 6, 1992, and in revised form November 9, 1992 This paper evaluates the effect of small differences in selenium exposure, within the safe range, on the glomerular vascular tufts of rats fed high-sucrose diets. In the first experiment male Wistar rats were housed in galvanized cages and were provided sucrose-based diets to induce a mild chronic insult to the microcirculation. One group of rats received the diet prepared to contain 0.10 mg Se/kg and another group 0.21 mg Se/kg. To assure that the galvanized metal cages were not influencing the results of the experiment this protocol was repeated in a second experiment wherein rats were housed in stainless steel cages. The levels of Se used supported normal activity of the long-term indicator of Se sufftciency, erythrocyte glutathione peroxidase. In both experiments rats fed diets containing 0.21 mg Se/kg had larger Bowman’s capsules (P < 0.01) and vascular tufts (P < 0.01). Vascular tufts from these rats also contained a higher proportion of open capillary lumen (P < O.Ol), contained less cytoplasmic and extracellular material (P < O.OOl), and had larger nuclei (P < 0.001) than those fed 0.10 mg Se/kg. A third study was designed to determine if the selenium-dependent differences in nuclear size were indicative of this being a site of incor- poration. Year-old rats subjected to the same protocol as those in the second experiment were given ‘%e, by injection into the femoral vein, to label the sites of incorporation. Glomeruli were purified and subjected to subcellular fractionation. Ninety percent of the radioactivity was associated with the crude nuclear fraction. Purification of the crude nu- clear fraction demonstrated that the radioactivity was associated with the nuclei. 0 1992 Academic Press, Inc. INTRODUCTION Selenium (Se) is required for maintaining capillary integrity but when the level of exposure is either too low or high the microvasculature suffers damage. Ani- mals foraging on plants grown in soils of low Se concentration and those exposed to environments with high levels of the element develop a wide array of patho- logical lesions due to the breakdown in capillary integrity (National Research Council, 1976). Attempts to determine the basis for the importance of Se in the maintenance of capillary integrity have not been successful. The use of Se defi- ciency and toxicity states to study this problem is too severe since both of these conditions produce widespread tissue damage that masks the primary effect of Se on microvessels. We have previously shown that rat retinal capillaries are sensitive to Se status when they are subjected to mild injury resulting from chronic exposure to elevated blood lipids, glucose, and insulin (Lockwood and Eckhert, 1992). Under these conditions supplementation with Se within the safe range (between deficiency and toxicity) protected the retinal capillaries from mild injury. The conditions of the experiment provided a means to study the effect of Se directly on the microcir- culation free from the confounding variables induced by secondary pathologically ’ To whom correspondence should be addressed at Department of Environmental Health Sciences, University of California, Los Angeles, CA 90024-1772. Fax: (310) 794-2106. 222 0014-4800/92 $5.00 Copyright 8 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.