Nonpeptide Angiotensin II Receptor Antagonists: In Vivo Inhibition of [125I-SAR1, ILE8]Angiotensin II Binding by Losartan, EXP597 and L-159,282 in Rats

Effects of losartan, L-159,282 and EXP597 on the in vivo binding of [125I-Sar1, Ile8]angiotensin II to kidney cortex and adrenal were examined in rats. Losartan, an AT1 receptor antagonist, completely blocked [125I-Sar1, Ile8]angiotensin II binding to the kidney cortex which contains only AT1 binding sites with an ID50 of 0.06 mg/kg. Losartan partially inhibited [125I-Sar1, Ile8]angiotensin II binding to the adrenal which contains equal amounts of AT1 and AT2 binding sites. Blockade by the AT1 receptor antagonist L-159,282 sufficiently increased the plasma levels of angiotensin II to block the AT2 receptor. EXP597 inhibited [125I-Sar1, Ile8]angiotensin II binding to the kidney cortex and adrenal almost totally with ID50S of 0.05 and 0.06 mg/kg, respectively. This result suggests that EXP597 exhibits almost equal binding affinity for AT1 and AT2 binding sites in vivo in rats.