Ticlopidine prevents renal disease progression in rats with reduced renal mass.
Functional and morphological studies were done in three groups of male Sprague-Dawley rats after removal of the right kidney and infarction of approximately five-sixths of the left. Group 1 received no specific therapy. Group 2 was treated with ticlopidine, 150 mg/kg per os, for 50 days starting 10 days after surgical ablation. Group 3 was given the thromboxane antagonist, GR 32191, 3 mg/kg b.i.d. orally for 50 days, like ticlopidine. Untreated Group 1 rats developed renal insufficiency, systemic hypertension, progressive proteinuria and glomerulosclerosis. In Group 2 treatment with ticlopidine was associated with less severe impairment of renal function. Proteinuria was significantly lower and animals were partially protected from the development of glomerulosclerosis. These animals had significantly prolonged skin bleeding time. In vitro ADP and arachidonic acid (AA)-induced platelet aggregation was inhibited. Systemic blood pressure was significantly lower than in controls. In Group 3 rats GR 32191 failed to influence progressive proteinuria and severity of glomerulosclerosis which were comparable to those in Group 1. Bleeding time was not prolonged, and in vitro platelet aggregation was inhibited only when AA was used as aggregating agent. Systemic blood pressure was not influenced. These studies suggest that a drug like ticlopidine, which has a broad spectrum of pharmacological actions on platelets and platelet-cell interactions, does retard the development of progressive renal injury when nephron number is reduced. Specific blocking of thromboxane A2 (TxA2) biological activity does not influence progressive renal disease in rats with remnant kidney.
Zoja
C
C
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Perico
N
N
Bergamelli
A
A
Pasini
M
M
Morigi
M
M
Dadan
J
J
Belloni
A
A
Bertani
T
T
Remuzzi
G
G
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001760:Bleeding Time; D001794:Blood Pressure / Q000187:drug effects; D006400:Hematocrit; D006538:Heptanoic Acids / Q000627:therapeutic use; D007238:Infarction; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013988:Ticlopidine / Q000627:therapeutic use*
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; C060013:vapiprost; D013988:Ticlopidine