Angiotensin II-mediated growth and antigrowth effects in cultured neonatal rat cardiac myocytes and fibroblasts
| Autor: | Pramod R. Saxena, H. A. A. Van Heugten, C. A. M. Van Kesteren, Maarten A.D.H. Schalekamp, Alexander H. J. Danser, Jos M. J. Lamers |
|---|---|
| Přispěvatelé: | Internal Medicine, Biochemistry |
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Pyridines Inositol Phosphates Biology Losartan chemistry.chemical_compound Angiotensin Receptor Antagonists Internal medicine Renin–angiotensin system medicine Myocyte Animals Rats Wistar Growth Substances Molecular Biology Cells Cultured Angiotensin II receptor type 1 Receptors Angiotensin Endothelin-1 Angiotensin II Myocardium Imidazoles Heart Fibroblasts Endothelin 1 Growth Inhibitors Rats Endocrinology chemistry Animals Newborn cardiovascular system Leucine Cardiology and Cardiovascular Medicine Thymidine hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Molecular and Cellular Cardiology, 2147-2157. Academic Press ISSUE=29;STARTPAGE=2147;ENDPAGE=2157;ISSN=0022-2828;TITLE=Journal of Molecular and Cellular Cardiology |
| ISSN: | 0022-2828 |
| Popis: | Angiotensin II (Ang II) stimulates cardiovascular growth and remodeling via AT1receptors. Recent experiments have shown that Ang II may also exert antiproliferative effects via AT2receptors. We studied the effects of Ang II on protein and DNA content and synthesis rate in unstimulated and endothelin-1 (ET-1)-stimulated neonatal rat cardiomyocytes and fibroblasts, isolated from 1–3-day-old Wistar strain pups. Total protein and total DNA, as well as [3H]leucine and [3H]thymidine incorporation were measured following incubation with either vehicle, Ang II, ET-1 or Ang II+ET-1, both in the presence or absence of the AT1receptor blocker losartan or the AT2receptor blocker PD123319. In myocytes, ET-1 increased total protein (+38% relative to control) as well as [3H]leucine (+66%) and [3H]thymidine (+77%) incorporation. Ang II did not affect any of these parameters, nor did it influence the ET-1-induced responses. However, in the presence of PD123319 Ang II stimulated [3H]leucine (+24%) and [3H]thymidine (+30%) incorporation. In fibroblasts, ET-1 and Ang II did not significantly affect total DNA and [3H]thymidine incorporation. Ang II tended to increase total protein in these cells, an effect which was significant only in the presence of PD123319 (+17%). Ang II stimulated [3H]leucine incorporation (+24%) in fibroblasts. This effect was absent with losartan and enhanced in the presence of PD123319. These data demonstrate that AT1receptor-mediated proliferative effects of Ang II in neonatal cardiac cells may become apparent only when its AT2receptor-mediated antigrowth effects are blocked. The net growth effect of Ang II therefore depends on the cellular AT1/AT2receptor ratio. Ang II does not appear to interfere with ET-1-induced effects. |
| Databáze: | OpenAIRE |
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