NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS - IN-VIVO INHIBITION OF [I-125-SAR(1),ILE(8)]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 [I -125-Sar(1),Ile(8)]angiotensin II to kidney cortex and adrenal were ex amined in rats. Losartan, an AT(1) receptor antagonist, completely blo cked [I-125-Sar(1),Ile(8)]angiotensin II binding to the kidney cortex which contains only AT(1) binding sites with an ID50 of 0.06 mg/kg. Lo sartan partially inhibited [I-125-Sar(1),Ile(8)]angiotensin II binding to the adrenal which contains equal amounts of AT(1) and AT(2) bindin g sites. Blockade by the AT(1) receptor antagonist L-159,282 sufficien tly increased the plasma levels of angiotensin II to block the AT(2) r eceptor. EXP597 inhibited [I-125-Sar(1),Ile(8)]angiotensin II binding to the kidney cortex and adrenal almost totally with ID(50)s of 0.05 a nd 0.06 mg/kg, respectively. This result suggests that EXP597 exhibits almost equal binding affinity for AT(1) and AT(2) binding sites in vi vo in rats.