Statins ameliorate endothelial barrier permeability changes in the cerebral tissue of streptozotocin-induced diabetic rats.
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.
Mooradian
Arshag D
AD
Division of Endocrinology, Diabetes and Metabolism, Saint Louis University Medical School, St. Louis, MO 63104, USA. mooradad@slu.edu
Haas
Michael J
MJ
Batejko
Oksana
O
Hovsepyan
Meri
M
Feman
Stephen S
SS
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001813:Blood-Retinal Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000187:drug effects*; D003326:Coronary Circulation; D003911:Dextrans; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D005464:Fluorobenzenes / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D009206:Myocardium; D011743:Pyrimidines / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012160:Retina / Q000503:physiopathology; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
D003911:Dextrans; D005456:Fluorescent Dyes; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C015219:fluorescein isothiocyanate dextran; D000068718:Rosuvastatin Calcium; D019821:Simvastatin; D016650:Fluorescein-5-isothiocyanate