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.