(Hypertension. 1996;28:104-108.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensin-(1-7) Inhibits Vascular Smooth Muscle Cell Growth
the Calhoun Research Laboratory, Department of Internal Medicine, Akron (Ohio) General Medical Center (E.J.F.); the Department of Cell Biology, The Research Institute of the Cleveland (Ohio) Clinic Foundation (G.M.C.); and the Hypertension Center, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (C.M.F., E.A.T.).
Correspondence to E. Ann Tallant, The Hypertension Center, The Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032.
Although angiotensin II (Ang II) and the heptapeptide Ang-(1-7) differ by only one amino acid, the two peptides produce different responses in vascular smooth muscle cells. We previously showed that Ang II stimulated phosphoinositide hydrolysis, whereas Ang II and Ang-(1-7) released prostaglandins. We now report that Ang II and Ang-(1-7) differentially modulate rat aortic vascular smooth muscle cell growth. Ang-(1-7) inhibited [3H]thymidine incorporation in response to stimulation by fetal bovine serum, platelet-derived growth factor, or Ang II. The reduction in serum-stimulated thymidine incorporation by Ang-(1-7) depended on the concentration of the heptapeptide over the range of 1 nmol/L to 1 µmol/L, with a maximal inhibition of 60% by 1 µmol/L Ang-(1-7). Ang-(1-7) also inhibited the serum-stimulated increase in cell number to a maximum of 77% by 1 µmol/L Ang-(1-7). The attenuation of serum-stimulated thymidine incorporation by Ang-(1-7) was unaffected by antagonists selective for angiotensin type 1 (AT1) or type 2 (AT2) receptors; however, [Sar1,Ile8]Ang II and [Sar1,Thr8]Ang II were effective antagonists, indicating that growth inhibition by Ang-(1-7) was a result of angiotensin receptor activation. In contrast, Ang II stimulated [3H]thymidine incorporation in cultured vascular smooth muscle cells over the same concentration range, with a maximal stimulation of 314% at 1 µmol/L Ang II. Ang II also increased the total number of cells (to 145% of control), suggesting that enhanced thymidine incorporation was associated with vascular smooth muscle cell proliferation. The AT1 antagonist losartan or L-158,809 but not AT2 antagonists blocked [3H]thymidine incorporation by Ang II. These results suggest that Ang-(1-7) and Ang II exhibit opposite effects on the regulation of vascular smooth muscle cell growth. The inhibition of proliferation by Ang-(1-7) appears to be mediated by a novel angiotensin receptor that is not inhibited by AT1 or AT2 receptor antagonists.
Key Words: angiotensin-(1-7) • angiotensin II • receptors, angiotensin II • muscle, smooth, vascular • growth
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