Protective effect of heparin on renal glomerular anionic sites of streptozotocin-injected rats.
Albuminuria at the rate of 500 micrograms/24 h was observed in rats treated with 50 mg/kg body wt. i.v. streptozotocin (STZ). When STZ was combined with heparin, administered twice daily (250 IU/kg subcutaneous injection) after 24 h following STZ injection, the daily urinary albumin excretion (U-AE) was less than half the amount found in non-heparinized rats (280.3 micrograms/24 h). The observation period in both instances was 8 weeks. When animals were permitted to develop albuminuria over the first 4 weeks, subsequent heparin administration for another 4 weeks lowered U-AE from 500 micrograms/24 h to less than half the amount (227.8 micrograms/24 h). A significantly negative correlation (P < 0.001) existed between U-AE and the number of anionic sites (AS) in the lamina rara externa of glomerular basement membranes, as visualized by electron microscopy. The number of AS per 1000 nm in STZ-injected rats (15.5 +/- 0.2) was lower than that in control rats (23.1 +/- 0.6); however, in heparinized animals, regardless of STZ, the values were not significantly different from normal. Heparin by itself had no effect on the number of AS in normal rats. All STZ-injected animals became hyperglycemic (400-550 mg/dl), but received no insulin. Heparin had no effect on plasma glucose levels. From these results, it is concluded that heparin suppressed both of an increase in U-AE and a decrease in AS count of glomerular basement membranes in STZ-injected rats.
Oshima
Y
Y
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Isogai
S
S
Mogami
K
K
Ohuchi
H
H
Ohe
K
K
D000419:Albuminuria; D000818:Animals; D000838:Anions; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004334:Drug Administration Schedule; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
D000838:Anions; D001786:Blood Glucose; D013311:Streptozocin; D006493:Heparin