Characterization of a new selective antagonist for angiotensin-(1-7), D-pro7-angiotensin-(1-7)

Hypertension. 2003 Mar;41(3 Pt 2):737-43. doi: 10.1161/01.HYP.0000052947.60363.24. Epub 2003 Jan 20.


Angiotensin-(1-7) [Ang-(1-7)] has biological actions that can often be distinguished from those of angiotensin II (Ang II). Recent studies indicate that the effects of Ang-(1-7) are mediated by specific receptor(s). We now report the partial characterization of a new antagonist selective for Ang-(1-7), D-Pro7-Ang-(1-7). D-Pro7-Ang-(1-7) (50 pmol) inhibited the hypertensive effect induced by microinjection of Ang-(1-7) [4+/-1 vs 21+/-2 mm Hg, 25 pmol Ang-(1-7) alone] into the rostral ventrolateral medulla without changing the effect of Ang II (16+/-2.5 vs 19+/-2.5 mm Hg after 25 pmol Ang II alone). At 10(-7) mol/L concentration, it completely blocked the endothelium-dependent vasorelaxation produced by Ang-(1-7) (10(-10) to 10(-6) mol/L) in the mouse aorta. The antidiuresis produced by Ang-(1-7) (40 pmol/100 g body weight) in water-loaded rats was also blocked by its analog [1 microg/100 g body weight; 3.08+/-0.8 vs 1.27+/-0.33 mL in Ang-(1-7)-treated rats]. D-Pro7-Ang-(1-7) at a molar ratio of 40:1 did not change the hypotensive effect of bradykinin. Moreover, D-Pro7-Ang-(1-7) did not affect the dipsogenic effect produced by intracerebroventricular administration of Ang II (11.4+/-1.15 vs 8.8+/-1.2 mL/h after Ang II) and did not show any demonstrable angiotensin-converting enzyme inhibitory activity in assays with the synthetic substrate Hip-His-Leu and rat plasma as a source of enzyme. Autoradiography studies with 125I-Ang-(1-7) in mouse kidney slices showed that D-Pro7-Ang-(1-7) competed for the binding of Ang-(1-7) to the cortical supramedullary region. In Chinese hamster ovary cells stably transfected with the AT1 receptor subtype, D-Pro7-Ang-(1-7) did not compete for the specific binding of 125I-Ang-II in concentrations up to 10(-6) mol/L. There was also no significant displacement of Ang II binding to angiotensin type 2 receptors in membrane preparations of adrenal medulla. These data indicate that D-Pro7-Ang-(1-7) is a selective antagonist for Ang-(1-7), which can be useful to clarify the functional role of this heptapeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / antagonists & inhibitors*
  • Angiotensin I / metabolism
  • Angiotensin I / pharmacology*
  • Angiotensin II / metabolism
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / physiology
  • Culture Techniques
  • Male
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar
  • Renal Agents / antagonists & inhibitors*
  • Renal Agents / metabolism
  • Vasodilation / drug effects


  • D-Pro7-Ang-(1-7)
  • Peptide Fragments
  • Renal Agents
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)