Mechanical strain and collagen potentiate mitogenic activity of angiotensin II in rat vascular smooth muscle cells.
The effects of extracellular matrix proteins and mechanical strain on the mitogenic activity of angiotensins I and II (AI and AII) were examined in cultured rat vascular smooth muscle (VSM) cells. VSM cells on various extracellular matrices were exposed to AII (1 microM) for 48 h. On plastic, AII induced only a 1.6-fold increase in [3H]thymidine incorporation, but on fibronectin- or type I collagen-coated plastic, the response to AII was enhanced from two- to fourfold. On a type I collagen-coated silicone elastomer, to which mechanical strain was applied, [3H]thymidine incorporation dramatically increased to a maximum of 53-fold. Dup 753 (10(-5) M) blocked the AII-induced increase in DNA synthesis. AI also increased DNA synthesis in VSM cells, and this response was also enhanced by mechanical strain. Mitogenic activity of AI was blocked by ramiprilat (10(-5) M), indicating that its mitogenic activity was via conversion to AII. The synergy between AII and strain was completely eliminated by neutralizing antibodies to PDGF AB (3 micrograms/ml). Furthermore, the mitogenic effect of AII in unstrained cells was also synergistic with submaximal concentrations of PDGF AB (1 ng/ml). Thus, the synergy between AII and mechanical strain probably results from synergism between AII and PDGF secreted in response to strain.
Sudhir
K
K
Division of Cardiology, University of California, San Francisco 94143.
Wilson
E
E
Chatterjee
K
K
Ives
H E
HE
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D005353:Fibronectins / Q000494:pharmacology; D005780:Gelatin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D005353:Fibronectins; D007093:Imidazoles; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D013777:Tetrazoles; D000804:Angiotensin II; C052549:ramiprilat; D005780:Gelatin; D003094:Collagen; D004247:DNA; D019808:Losartan; D017257:Ramipril; D013936:Thymidine