Effects of losartan and PD123319 on antigensin II-induced proto-oncogene expression and protein synthesis in cultured neonatal rat cardiac myocytes

Hunan Yi Ke Da Xue Xue Bao. 1997;22(4):283-6.

Abstract

To study the effects of specific angiotension II (Ang II) receptor, type-1 (AT1) antagonist (Losartan) and type-2 (AT2) antagonist (PD123319), on Ang II-induced proto-oncogene expression and synthesis of RNA and protein in neonatal rat cardiac myocytes, we used respectively [3H]-uridine and [3H]-leucine incorporation to measure the rate of RNA and protein synthesis, and analyzed the c-myc mRNA level by Northern blot. We found that an acceleration in the rate of RNA and protein synthesis was observed when exposed to 2.5 x 10(-6) mol.L-1 [Sar1] Ang II for 24 h (P < 0.01). Losartan inhibited the action in a dose-dependent manner. The level of c-myc mRNA was up-regulated to 340% of control by 2.5 x 10(-6) mol.L-1 Ang II, and Losartan (10(-5) mol.L-1) suppressed the increase of c-myc mRNA stimulated by Ang II. PD123319 showed similar inhibition on Ang II-induced RNA and protein synthesis, but did not inhibit c-myc expression. Thus, Ang II-stimulated expression of c-myc is mainly mediated by AT1 receptors, and contributes to cardiac myocyte hypertrophy while AT2 receptors are involved in mediation of cellular growth without altering of c-myc expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Animals
  • Animals, Newborn
  • Cell Division
  • Cells, Cultured
  • Gene Expression
  • Imidazoles / pharmacology*
  • Losartan / pharmacology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Pyridines / pharmacology*
  • RNA, Messenger / genetics
  • Rats
  • Receptor, Angiotensin, Type 1

Substances

  • Angiotensin Receptor Antagonists
  • Imidazoles
  • Proto-Oncogene Proteins c-myc
  • Pyridines
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • PD 123319
  • Losartan