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The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells.
J Clin Invest. 1995 Feb; 95(2):651-7.JCI

Abstract

Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2-receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose-dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor.

Authors+Show Affiliations

Department of Pharmacology, University of Kiel, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7860748

Citation

Stoll, M, et al. "The Angiotensin AT2-receptor Mediates Inhibition of Cell Proliferation in Coronary Endothelial Cells." The Journal of Clinical Investigation, vol. 95, no. 2, 1995, pp. 651-7.
Stoll M, Steckelings UM, Paul M, et al. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest. 1995;95(2):651-7.
Stoll, M., Steckelings, U. M., Paul, M., Bottari, S. P., Metzger, R., & Unger, T. (1995). The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. The Journal of Clinical Investigation, 95(2), 651-7.
Stoll M, et al. The Angiotensin AT2-receptor Mediates Inhibition of Cell Proliferation in Coronary Endothelial Cells. J Clin Invest. 1995;95(2):651-7. PubMed PMID: 7860748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. AU - Stoll,M, AU - Steckelings,U M, AU - Paul,M, AU - Bottari,S P, AU - Metzger,R, AU - Unger,T, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 651 EP - 7 JF - The Journal of clinical investigation JO - J Clin Invest VL - 95 IS - 2 N2 - Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2-receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose-dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/7860748/The_angiotensin_AT2_receptor_mediates_inhibition_of_cell_proliferation_in_coronary_endothelial_cells_ L2 - https://doi.org/10.1172/JCI117710 DB - PRIME DP - Unbound Medicine ER -