Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells

Mizuo Mifune, Hiroyuki Sasamura, Ryoko Shimizu, Hitoshi Miyazaki, Takao Saruta

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the angiotensin II type 1 (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role has not yet been fully defined. The aim of the present study was to examine the effects of stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells. Retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. The treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity but caused a modest (30% to 50%) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148±17% of control at 48 hours, P<0.05), which was completely inhibited by the AT2 receptor antagonist PD123319, unaffected by the AT1 receptor antagonist losartan, and attenuated by treatment with pertussis toxin or G(αi) antisense oligonucleotides. Interestingly, studies in other cell lines demonstrated that CGP42112A caused similar results in transfected mesangial cells but had essentially opposite effects in fibroblasts (NIH-3T3-AT2). These results suggest that AT2 receptor stimulation can increase collagen synthesis in vascular smooth muscle cells via a G(αi-mediated) mechanism and provide evidence for heterogeneity in the effects of AT2 receptor stimulation in different tissues.

Original languageEnglish
Pages (from-to)845-850
Number of pages6
JournalHypertension
Volume36
Issue number5
Publication statusPublished - 2000

Fingerprint

Angiotensin Type 2 Receptor
Vascular Smooth Muscle
Smooth Muscle Myocytes
Collagen
Collagen Receptors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Type 1 Receptor
Protein Tyrosine Phosphatases
Mesangial Cells
Losartan
Antisense Oligonucleotides
Mitogen-Activated Protein Kinase 1
Pertussis Toxin
Angiotensin II
Extracellular Matrix
Fibroblasts
Cell Line
Genes
CGP 42112A

Keywords

  • Angiotensin II
  • Collagen
  • Fibroblasts
  • Muscle
  • Receptor, angiotensin II
  • Smooth, vascular

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells. / Mifune, Mizuo; Sasamura, Hiroyuki; Shimizu, Ryoko; Miyazaki, Hitoshi; Saruta, Takao.

In: Hypertension, Vol. 36, No. 5, 2000, p. 845-850.

Research output: Contribution to journalArticle

Mifune, M, Sasamura, H, Shimizu, R, Miyazaki, H & Saruta, T 2000, 'Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells', Hypertension, vol. 36, no. 5, pp. 845-850.
Mifune, Mizuo ; Sasamura, Hiroyuki ; Shimizu, Ryoko ; Miyazaki, Hitoshi ; Saruta, Takao. / Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells. In: Hypertension. 2000 ; Vol. 36, No. 5. pp. 845-850.
@article{12fff80a636e43bcafe4b0c42d6e1e8e,
title = "Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells",
abstract = "Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the angiotensin II type 1 (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role has not yet been fully defined. The aim of the present study was to examine the effects of stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells. Retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. The treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity but caused a modest (30{\%} to 50{\%}) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148±17{\%} of control at 48 hours, P<0.05), which was completely inhibited by the AT2 receptor antagonist PD123319, unaffected by the AT1 receptor antagonist losartan, and attenuated by treatment with pertussis toxin or G(αi) antisense oligonucleotides. Interestingly, studies in other cell lines demonstrated that CGP42112A caused similar results in transfected mesangial cells but had essentially opposite effects in fibroblasts (NIH-3T3-AT2). These results suggest that AT2 receptor stimulation can increase collagen synthesis in vascular smooth muscle cells via a G(αi-mediated) mechanism and provide evidence for heterogeneity in the effects of AT2 receptor stimulation in different tissues.",
keywords = "Angiotensin II, Collagen, Fibroblasts, Muscle, Receptor, angiotensin II, Smooth, vascular",
author = "Mizuo Mifune and Hiroyuki Sasamura and Ryoko Shimizu and Hitoshi Miyazaki and Takao Saruta",
year = "2000",
language = "English",
volume = "36",
pages = "845--850",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Angiotensin II Type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells

AU - Mifune, Mizuo

AU - Sasamura, Hiroyuki

AU - Shimizu, Ryoko

AU - Miyazaki, Hitoshi

AU - Saruta, Takao

PY - 2000

Y1 - 2000

N2 - Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the angiotensin II type 1 (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role has not yet been fully defined. The aim of the present study was to examine the effects of stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells. Retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. The treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity but caused a modest (30% to 50%) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148±17% of control at 48 hours, P<0.05), which was completely inhibited by the AT2 receptor antagonist PD123319, unaffected by the AT1 receptor antagonist losartan, and attenuated by treatment with pertussis toxin or G(αi) antisense oligonucleotides. Interestingly, studies in other cell lines demonstrated that CGP42112A caused similar results in transfected mesangial cells but had essentially opposite effects in fibroblasts (NIH-3T3-AT2). These results suggest that AT2 receptor stimulation can increase collagen synthesis in vascular smooth muscle cells via a G(αi-mediated) mechanism and provide evidence for heterogeneity in the effects of AT2 receptor stimulation in different tissues.

AB - Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the angiotensin II type 1 (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role has not yet been fully defined. The aim of the present study was to examine the effects of stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells. Retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. The treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity but caused a modest (30% to 50%) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148±17% of control at 48 hours, P<0.05), which was completely inhibited by the AT2 receptor antagonist PD123319, unaffected by the AT1 receptor antagonist losartan, and attenuated by treatment with pertussis toxin or G(αi) antisense oligonucleotides. Interestingly, studies in other cell lines demonstrated that CGP42112A caused similar results in transfected mesangial cells but had essentially opposite effects in fibroblasts (NIH-3T3-AT2). These results suggest that AT2 receptor stimulation can increase collagen synthesis in vascular smooth muscle cells via a G(αi-mediated) mechanism and provide evidence for heterogeneity in the effects of AT2 receptor stimulation in different tissues.

KW - Angiotensin II

KW - Collagen

KW - Fibroblasts

KW - Muscle

KW - Receptor, angiotensin II

KW - Smooth, vascular

UR - http://www.scopus.com/inward/record.url?scp=0033679159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033679159&partnerID=8YFLogxK

M3 - Article

C2 - 11082154

AN - SCOPUS:0033679159

VL - 36

SP - 845

EP - 850

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -