Role of hypertension and coagulation in the progressive glomerulopathy of rats with subtotal renal ablation.
Administration of heparin to rats with 1 3/4 nephrectomy prevents the development of glomerulosclerosis, hypertension and retards the decrease in renal function seen in these rats. To further define the role of hypertension and/or coagulation in the pathogenesis of the glomerulopathy seen in this model we studied several groups of rats with 1 3/4 nephrectomy: (1) a control group; (2) a group receiving a 'high dose' of acetylsalicylic acid (50 mg/kg) plus dipyridamole (10 mg/kg); (3) a group receiving a 'low' dose (5 mg/kg body weight) of acetylsalicylic acid alone; (4) a group receiving OKY 1581, an inhibitor of thromboxane synthesis; (5) a group treated with antihypertensive medications; (6) a group receiving heparin subcutaneously twice daily, and (7) a group given oral Coumadin. Drugs in all groups were administered daily for 4 weeks. All treated groups had a decrease in blood pressure (BP), in the ratio of heart weight to body weight, in BUN levels and had fewer abnormal glomeruli. The effects of acetylsalicylic acid alone, of acetylsalicylic acid plus dipyridamole, and OKY 1581 may be due to inhibition of platelet aggregation and intraglomerular thrombosis, with the fall in BP being the consequence of improved renal function. On the other hand, the decrease in BP may be related to a primary effect of these drugs. The lower BP in turn may play a role in slowing the progression of renal disease and improving the renal histology in the treated groups.
Department of Medicine, Washington University School of Medicine, St. Louis, Mo.
M L
ML
Purkerson
J H
JH
Joist
J
J
Yates
S
S
Klahr
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D005260:Female; D005921:Glomerulonephritis / Q000517:prevention & control*; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control*; D006977:Hypertension, Renal / Q000517:prevention & control*; D008689:Methacrylates / Q000627:therapeutic use; D009392:Nephrectomy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D000959:Antihypertensive Agents; D008689:Methacrylates; D010975:Platelet Aggregation Inhibitors; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D013930:Thromboxane-A Synthase