ACE inhibition and fibroblast growth factor in cultured human vascular smooth muscle

The effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril at, and basic fibroblast growth factor (bFGF) on DNA synthesis and expressi on of ACE mRNA were examined in human vascular smooth muscle cells cultured from saphenous vein and internal mammary artery. DNA synthesis was estimated using H-3-thymidine uptake, and ACE mRNA was es timated by rt-PCR. Enalaprilat (0.125 mu g/ml, 48 h) decreased H-3-thymidin e uptake to 66 +/- 12% (SE) of the control without enalaprilat (p < 0.05). Basic FGF (10 ng/ml, 24 h) increased uptake by 41 +/- 12% (p < 0.05) while enalaprilat pretreatment (24 h) decreased uptake to 56 +/- 12% of this augm ented value (p < 0.025). Basic FGF increased ACE mRNA, a process that was t ime dependent with an approximately 50% increase after 24 h exposure. Pre-e xposure to enalaprilat (24 h) before bFGF reduced ACE mRNA to approximately 50% of that found in the presence of bFGF alone. The results indicate that ACE mRNA is present in human vascular smooth musc le cells and that exposure to an ACE inhibitor reduces DNA synthesis. Basic FGF stimulates DNA synthesis and ACE mRNA expression, and both of these ef fects are reduced by an ACE inhibitor. The results are consistent with the effects of bFGF being exerted through, or alternatively in concert with, an giotensin II. Further, they suggest that ACE inhibition can reduce the acti vity of the renin-angiotensin system by inhibiting the production of ACE, o r at least the expression of ACE mRNA, in addition to producing enzyme inhi bition at the ACE level.