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 n ot be ruled out, the effect of the ATI antagonist, losartan (L), on th e course of ablation nephropathy was compared wit that of PD123319 (PD ), an AT2 antagonist. Wistar rats underwent surgical ablation of 5/6 o f 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 w ith PD alone. The drugs were administered in drinking water and rats d rinking 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% i n PD (no significant difference). The rats drinking L have a lower blo od pressure, proteinuria and glomerulosclerosis score, and higher crea tinine clearance than control and PD rats, again with no difference be tween 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 activit y was elevated only in both L groups. In conclusion, the beneficial ef fect of the AT1-receptor blocker L was again confirmed. AT2 receptors are obviously not involved in the detrimental effect of ANGII on the c ourse of ablation nephropathy.