PDGF-BB-induced DNA synthesis is delayed by angiotensin II in vascular smooth muscle cells.
The interaction of ANG II with platelet-derived growth factor (PDGF)-BB-induced DNA synthesis was studied in cultured rat aortic smooth muscle cells. PDGF-BB-induced DNA synthesis was delayed (approximately 6-8 h) by ANG II as shown by a time-course experiment. Losartan, an AT1-receptor antagonist, blocked the transient inhibitory effect of ANG II, whereas the AT2-receptor antagonist PD-123319 had no effect. Autocrine- or paracrine-acting transforming growth factor-beta 1 (TGF-beta 1), believed to be a mediator of ANG II-induced inhibitory effects, was not responsible for the delay of PDGF-BB-induced DNA synthesis, because a potent TGF-beta 1 neutralizing antibody could not reverse this effect of ANG II, nor was the delay of the PDGF-BB effect caused by inhibition of PDGF-beta-receptor phosphorylation as shown by Western blot analysis of immunoprecipitated PDGF-beta receptor. In conclusion, our results show that ANG II can exert a transient inhibitory effect on PDGF-BB-induced proliferation via the AT1 receptor.
Dahlfors
G
G
Department of Cell Biology, Faculty of Health Science, University of Linköping, Sweden.
Chen
Y
Y
Wasteson
M
M
Arnqvist
H J
HJ
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077214:Becaplermin; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004347:Drug Interactions; D019808:Losartan / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000925:Anticoagulants; D000959:Antihypertensive Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077214:Becaplermin; D019808:Losartan