Lack of a Beneficial Effect of PD123319, an AT2-Angiotensin Receptor Antagonist, on the Course of Ablation Nephropathy in the Rat

Since angiotensin II (ANGII) AT1-receptor antagonists have been shown to possess a beneficial effect on the course of ablation nephropathy, and since the possibility that AT2-receptors are also involved could not be ruled out, the effect of the AT1 antagonist, losartan (L), on the course of ablation nephropathy was compared wit that of PD123319 (PD), an AT2 antagonist. Wistar rats underwent surgical ablation of 5/6 of their renal parenchyma (5/6NX) and for the next 8 weeks were treated with either L alone (5 mg/kg/day), or with L + PD (10 mg/kg/day) or with PD alone. The drugs were administered in drinking water and rats drinking pure water served as controls. Whereas in both groups drinking L the survival rate was 100%, it was only 60% in controls and 66.6% in PD (no significant difference). The rats drinking L have a lower blood pressure, proteinuria and glomerulosclerosis score, and higher creatinine clearance than control and PD rats, again with no difference between these two. Cardiac and kidney remnant hypertrophy was completely abolished in both L groups, whereas it was distinctly present in the other 2 groups without a difference between them. Plasma renin activity was elevated only in both L groups. In conclusion, the beneficial effect of the AT1-receptor blocker L was again confirmed. AT2 receptors are obviously not involved in the detrimental effect of ANGII on the course of ablation nephropathy.