Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors

Brain Res Bull. 1994;35(4):293-8. doi: 10.1016/0361-9230(94)90104-x.


In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Amino Acid Sequence
  • Angiotensin I
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Angiotensin Receptor Antagonists
  • Animals
  • Blood Pressure / drug effects
  • Diuresis / drug effects
  • Female
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Injections, Intraventricular
  • Male
  • Medulla Oblongata / drug effects
  • Molecular Sequence Data
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Angiotensin / drug effects
  • Receptors, Angiotensin / metabolism*
  • Uterine Contraction / drug effects


  • 7-Ala-angiotensin (1-7)
  • Angiotensin Receptor Antagonists
  • Peptide Fragments
  • Receptors, Angiotensin
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)