Nonpeptide angiotensin II receptor antagonists: in vivo inhibition of [125I-Sar1,Ile8]angiotensin II binding by losartan, EXP597 and L-159,282 in rats

Clin Exp Hypertens. 1996 Feb;18(2):189-200. doi: 10.3109/10641969609081764.

Abstract

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.

MeSH terms

  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / metabolism
  • Angiotensin Receptor Antagonists*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Biphenyl Compounds / pharmacology*
  • Imidazoles / pharmacology*
  • Losartan
  • Male
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology
  • Tetrazoles / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Imidazoles
  • Pyridines
  • Sulfonamides
  • Tetrazoles
  • Angiotensin II
  • MK 996
  • EXP 597
  • angiotensin II, Sar(1)-Ile(5)-
  • Losartan