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(Hypertension. 1997;29:388.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

Bovine Aortic Endothelial Cells Contain an Angiotensin-(1–7) Receptor

E. Ann Tallant; Xiaowei Lu; Randi B. Weiss; Mark C. Chappell; Carlos M. Ferrario

From The Hypertension Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.

Correspondence to E. Ann Tallant, The Hypertension Center, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1032

Angiotensin-(1–7) is a novel peptide of the reninangiotensin system that counteracts the pressor and proliferative responses to angiotensin II. We now report that cultured bovine aortic endothelial cells contain a saturable, high-affinity [¹²⁵I]angiotensin-(1–7) binding site with an affinity of 19.3±10.7 nmol/L and a density of 1351±710 fmol/mg protein. Angiotensin-(1–7) competed at a second lower-affinity site, with an IC₅₀ of 2.9 µmol/L. The high-affinity angiotensin II receptor antagonist sarcosine¹-isoleucine⁸-angiotensin II blocked [¹²⁵I]angiotensin-(1–7) binding to bovine aortic endothelial cells at both a high-(IC₅₀=1.3 nmol/L) and a low-affinity (IC₅₀=6.2 µmol/L) binding site. In contrast, D-alanine⁷-angiotensin-(1–7) completely blocked [¹²⁵I]angiotensin-(1–7) binding, with an IC₅₀ of 19.8 nmol/L, suggesting that D-alanine⁷-angiotensin-(1–7) may selectively block responses to angiotensin-(1–7) in endothelial cells. Neither the AT₁ antagonist losartan nor the AT₂ antagonist PD 123319 exhibited significant competition for [¹²⁵I]angiotensin-(1–7) binding to endothelial cells isolated from bovine aorta, in agreement with the absence of detectable mRNAs encoding typical angiotensin receptor subtypes 1 or 2 (AT₁ or AT₂). Angiotensin II also competed for [¹²⁵I]angiotensin-(1–7) binding to bovine aortic endothelial cells; however, the relative affinity was 13-fold lower than angiotensin-(1–7), suggesting a preference for angiotensin-(1–7) over angiotensin II. These results demonstrate that bovine aortic endothelial cells contain a unique non-AT₁, non-AT₂ angiotensin receptor that preferentially binds angiotensin-(1–7).

Key Words: angiotensin-(1–7) • angiotensin II • angiotensin receptor subtypes • endothelium • vascular

Abbreviations: ACE = angiotensin-converting enzyme • Ang = angiotensin • AT₁, AT₂ = angiotensin receptor subtype 1, subtype 2 • BAEC = bovine aortic endothelial cell(s) • DMEM = Dulbecco's modified Eagle's medium • FBS = fetal bovine serum • HFBA = heptafluorobutyric acid • RT-PCR = reverse-transcribed PCR • SHR = spontaneously hypertensive rat(s) • VSMC = vascular smooth muscle cell(s)

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