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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 μg/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 with125 I–Ang-(1–7) in mouse kidney slices showed thatd -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 of125 I–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 thatd -Pro7 -Ang-(1–7) is a selective antagonist for Ang-(1–7), which can be useful to clarify the functional role of this heptapeptide.

Characterization of a New Selective Antagonist for Angiotensin-(1–7), d -Pro 7 -Angiotensin-(1–7)

Characterization of a New Selective Antagonist for Angiotensin-(1–7), d -Pro ⁷ -Angiotensin-(1–7)