PMID- 11346891
OWN - NLM
STAT- MEDLINE
DCOM- 20011101
LR  - 20191104
IS  - 0379-0355 (Print)
IS  - 0379-0355 (Linking)
VI  - 22
IP  - 10
DP  - 2000 Dec
TI  - Induction of cardiac fibrosis by angiotensin II.
PG  - 709-23
AB  - The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2 
      (AT2) to angiotensin II-induced changes in collagen secretion and production were 
      studied using the specific angiotensin receptor AT1 and AT2 antagonists 
      telmisartan and P-186. The role of the renin-angiotensin system and its 
      interaction with transforming growth factor-beta 1 (TGF-beta 1) in collagen 
      deposition in cardiac fibroblasts in relation to the development of myocardial 
      fibrosis is also discussed. Cardiac fibroblasts (from normal male adult rats) 
      from passage 2 were cultured to confluency and incubated in the presence of 
      angiotensin II (ANG II) in a concentration range of 10(-10)-10(-6) M in 
      serum-free Dulbecco's MEM medium for 24 h. Collagen production and secretion were 
      assayed by [3H]-proline incorporation and noncollagen production and secretion 
      were also analyzed. ANG II dose-dependently increased collagen secretion and 
      production in rat adult cardiac fibroblasts in culture. Noncollagen secretion and 
      production were also concentration-dependently increased by ANG II. Addition of 
      100 nmol/l ANG II increased (p < 0.01) collagen secretion and production by 75 
      +/- 6 (SEM) and 113 +/- 23%, respectively, and noncollagen secretion and 
      production by 65 +/- 6 and 57 +/- 16%, respectively. Pretreatment of cardiac 
      fibroblasts with telmisartan completely blocked the ANG II-induced increase in 
      collagen secretion (p < 0.001) and production (p < 0.05) and in noncollagen 
      secretion (p < 0.01) and production (p < 0.01). P-186 had no effect on the ANG 
      II-induced increase in collagen secretion and production. Addition of telmisartan 
      and P-186 did not affect collagen secretion and production in basal cardiac 
      fibroblasts. TGF-beta 1 also concentration- and time-dependently increased the 
      secretion and production of collagen in cardiac fibroblasts. Our data demonstrate 
      that the effects of ANG II on collagen secretion and production in adult rat 
      cardiac fibroblasts in culture are AT1-receptor mediated since they were 
      abolished by the specific AT1-receptor antagonist telmisartan but not by the 
      specific AT2-receptor antagonist P-186. The ability of ANG II to induce collagen 
      synthesis in cardiac fibroblasts may be mediated by increased TGF-beta 1 
      production.
FAU - Lijnen, P J
AU  - Lijnen PJ
AD  - Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and 
      Cardiovascular Research, Faculty of Medicine, University of Leuven, Leuven, 
      Belgium. paul.lijnen@med.kuleuven.ac.be
FAU - Petrov, V V
AU  - Petrov VV
FAU - Fagard, R H
AU  - Fagard RH
LA  - eng
PT  - Journal Article
PL  - Spain
TA  - Methods Find Exp Clin Pharmacol
JT  - Methods and findings in experimental and clinical pharmacology
JID - 7909595
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9007-34-5 (Collagen)
RN  - E7199S1YWR (Lisinopril)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - *Angiotensin Receptor Antagonists
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Benzimidazoles/pharmacology
MH  - Benzoates/pharmacology
MH  - Cells, Cultured
MH  - Collagen/*biosynthesis/metabolism
MH  - Culture Media, Serum-Free
MH  - Dose-Response Relationship, Drug
MH  - Fibroblasts/cytology/*drug effects/metabolism
MH  - Fibrosis
MH  - Lisinopril/pharmacology
MH  - Male
MH  - Myocardium/cytology/*metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Telmisartan
MH  - Time Factors
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 2001/05/12 10:00
MHDA- 2001/11/03 10:01
CRDT- 2001/05/12 10:00
PHST- 2001/05/12 10:00 [pubmed]
PHST- 2001/11/03 10:01 [medline]
PHST- 2001/05/12 10:00 [entrez]
AID - 802287 [pii]
AID - 10.1358/mf.2000.22.10.802287 [doi]
PST - ppublish
SO  - Methods Find Exp Clin Pharmacol. 2000 Dec;22(10):709-23. doi: 
      10.1358/mf.2000.22.10.802287.