Effects of omapatrilat on endothelin-1-induced proliferation and synthesis of cardiac fibroblasts / 中国应用生理学杂志

ABSTRACT

<p><b>AIM</b>To investigate the effects of omapatrilat (OMA) on endothelin-1-induced proliferation of cardiac fibroblasts (CFs).</p><p><b>METHODS</b>Isolated and cultured CFs from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups (1) Control, (2) ET-1, (3) OMA, (4) ET-1 + OMA 10(-9) mol/L, (5) ET-1 + OMA 10(-8) mol/L, (6) ET-1 + OMA 10(-7) mol/L and (7) ET-1 + OMA 10(-6) mol/L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was measured by colorimetry.</p><p><b>RESULTS</b>10(-7) mol/L ET-1 significantly increased A490 value and [3H]-Pro incorporation and decreased NO secretion compared with the control group (P < 0.01). 10(-9)-10(-6) mol/L OMA inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P < 0.01 vs. ET-1). In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by l0(-6) mol/L OMA (P < 0.01 vs. ET-1 and control).</p><p><b>CONCLUSION</b>OMA can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.</p>