Effect of Angiotensin Converting Enzyme Inhibitor on Collagen Production by Cultured Mesangial Cells

Abstract

Cultured mesangial cells (MC) express renin mRNA and generate angiotensin I, supporting the action of local renin-angiotensin system. Also angiotensin II may act like a growth factor and was reported to increase collagen production (CP) in cultured MC. Angiotensin converting enzyme inhibitor is suggested to attenuate development and advancement of glomerulosclerosis, mainly with its hemodynamic effects. Therefore, we investigated the direct effects of enalapril (E) on CP by cultured MC. Rat MC were cultured in DMEM media alone, or containing high glucose (HG: 25 mM) or soluble immune complex (IC) prepared with bovine gamma globulin (BGG) and anti-BGG, with or without E (0.2 ug/ml). CP was determined after 24 h by [3H] proline incorporation method. E significantly reduced CP by 43% in medium as compared with control (C)(C: 37,210±4,200 vs C+E: 21,350 ± 5,080 cpm/well, p<0.01). CP in medium increased in the presence of HG (123% of C) or IC (147% of C), which was, however, prevented with E (HG + E: 105% of C, IC+E: 116% of C). There were no differences of CP in cell layer between C (3,490±220 cpm/well) and C+E (3,340±190 cpm/well), and also no changes after, addition of E in HG or IC groups. In conclusion, E directly attenuates CP by MC, even in the presence of HG or IC, independently of its hemodynamic effects.