RT Journal Article
SR Electronic
T1 HR 720, A Novel Angiotensin Receptor Antagonist Inhibits the Angiotensin II-Induced Trophic Effects, Fibronectin Release and Fibronectin-EIIIA+ Expression in Rat Aortic Vascular Smooth Muscle Cells in Vitro
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 447
OP 453
VO 280
IS 1
A1 F. W. Dunn
A1 M.-H. Roux
A1 F. Farhadian
A1 K. Sabri
A1 C. Ossart
A1 J. L. Samuel
A1 L. Rappaport
A1 G. Hamon
YR 1997
UL http://jpet.aspetjournals.org/content/280/1/447.abstract
AB The aim of this study was to evaluate the direct trophic effects of angiotensin II (AII) on rat vascular smooth muscle cells obtained from a single cellular isolate. Cell volume, protein synthesis, fibronectin (FN) release and FN-EIIIA+ mRNA isoform expression were analyzed in parallel. The effects of HR 720, a novel AT1 angiotensin receptor antagonist with some AT2 receptor affinity, were compared with those of selective AT1 antagonist EXP 3174. Both HR 720 and EXP 3174 inhibited in a concentration-dependent manner the maximum increase in cell volume induced by 10−9 M Sar1-AII (IC50 = 0.49 × 10−9 M and 0.79 × 10−9 M, respectively). Maximum [3H]leucine incorporation was also achieved at 10−9 M AII. HR 720 blocked the increase in protein synthesis with potency similar to EXP 3174; the respective IC50 values were 1.04 × 10−9 M and 1.36 × 10−9 M. AII dose-dependently increased FN release, which was also equally inhibited by about 50% with both compounds at 10−8 M. Furthermore, AII enhanced FN-EIIIA+ mRNA in rat vascular smooth muscle cells (VSMC), which indicated a modulation of FN isoform expression which was inhibited by angiotensin II antagonists. In conclusion, AII induced parallel and concentration-dependent increases in cell volume, protein synthesis, FN release and FN-EIIIA+ mRNA expression in vascular smooth muscle cells. These effects appeared to be essentially mediated by AT1 receptor stimulation as indicated by the equal inhibitory effects of HR 720 and EXP 3174. The American Society for Pharmacology and Experimental Therapeutics