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Diabetes 54:2977-2982, 2005
© 2005 by the American Diabetes Association, Inc.

Statins Ameliorate Endothelial Barrier Permeability Changes in the Cerebral Tissue of Streptozotocin-Induced Diabetic Rats

Arshag D. Mooradian1, Michael J. Haas1, Oksana Batejko1, Meri Hovsepyan1, and Stephen S. Feman2

1 Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri
2 Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, Missouri

Statins may have favorable effects on endothelial barrier function. The effect of rosuvastatin and simvastatin therapy (10 mg/kg) for 5 weeks on blood-brain barrier (BBB), blood-retinal barrier (BRB), and cardiac muscle permeability of streptozotocin-induced diabetic rats was studied. The size-selective permeability of different vascular beds to a group of fluorescein isothiocyanate dextrans of varying molecular weights was measured. The volume of distribution of 250-, 70-, and 40-kDa dextrans in the cerebral tissue of diabetic rats were significantly increased. The volume of distribution of these dextrans in cerebral tissue was normalized by both statins. Diabetes did not significantly alter the BRB, but both statins decreased the volume of distribution of 70- and 40-kDa dextrans in the retina. The volume of distribution of 40 kDa in cardiac muscle was increased in diabetes, and this change was prevented with statin treatment. Treatment with rosuvastatin and mevalonate (150 mg/kg in drinking water for 5 weeks) did not alter the volume of distribution measurements. We concluded that 1) diabetes in rats is associated with significant changes in the BBB permeability; 2) statin treatment improves the endothelial barrier function in cerebral tissue, retina, and cardiac muscle; and 3) this statin effect could not be attributed to HMGCoA reductase inhibition.

Address correspondence and reprint requests to Arshag D. Mooradian, MD, Division of Endocrinology, Saint Louis University Medical School, 1402 South Grand Blvd., St. Louis, MO 63104. E-mail: mooradad{at}slu.edu

Abbreviations: BBB, blood-brain barrier; BRB, blood-retinal barrier; FITC, fluorescein isothiocyanate


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Copyright © 2005 by the American Diabetes Association.