ACE inhibition and fibroblast growth factor in cultured human vascular smooth muscle.
The effects of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, and basic fibroblast growth factor (bFGF) on DNA synthesis and expression of ACE mRNA were examined in human vascular smooth muscle cells cultured from saphenous vein and internal mammary artery. DNA synthesis was estimated using 3H-thymidine uptake, and ACE mRNA was estimated by rt-PCR. Enalaprilat (0.125 microg/ml, 48 h) decreased 3H-thymidine 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 augmented value (p < 0.025). Basic FGF increased ACE mRNA, a process that was time dependent with an approximately 50% increase after 24 h exposure. Pre-exposure 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 muscle cells and that exposure to an ACE inhibitor reduces DNA synthesis. Basic FGF stimulates DNA synthesis and ACE mRNA expression, and both of these effects are reduced by an ACE inhibitor. The results are consistent with the effects of bFGF being exerted through, or alternatively in concert with, angiotensin II. Further, they suggest that ACE inhibition can reduce the activity of the renin-angiotensin system by inhibiting the production of ACE, or at least the expression of ACE mRNA, in addition to producing enzyme inhibition at the ACE level.
Tang
L
L
Department of Cardiology, Royal Perth Hospital, Western Australia, Australia.
Both
K
K
Taylor
R
R
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D017931:DNA Primers / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects; D015773:Enalaprilat / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D017931:DNA Primers; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D004247:DNA; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D013936:Thymidine