Thromboxane A2 receptor blockade improves renal function and histopathology in the post-obstructive kidney.

To elucidate the role of the vasoconstrictor thromboxane A2(TXA2) in post-obstructive nephropathy, we examined the effect of the TXA2 receptor antagonist GR32191(GR) on renal function and histopathology in the post-obstructed kidney (POK) in rats. Rats pre-treated with 3 or 6 mg/kg i.p. of GR prior to ureteral obstruction and maintained on b.i.d. doses of GR were compared to vehicle-treated and sham-operated controls. Renal hemodynamic, clearance and excretory function were assessed in each kidney following relief of 24 hours of unilateral ureteral obstruction. The histology of each kidney was evaluated. Mean clearances of inulin for the POK were significantly greater in the treated rats (0.42 +/- 0.06 ml/min at 6 mg/kg) than in controls (0.13 +/- 0.04 ml/min) and a dose-response effect was observed (P < 0.05). Paraaminohippurate clearance was increased by > 150% and renal vascular resistance was reduced by 50% in GR treated animals compared with controls (P < 0.05). Histopathologic findings in the untreated POK were typical of early obstruction. In the GR treated groups these changes were much less severe. These data support an important role for TXA2 in the pathogenesis of post-obstructive nephropathy.