The effect of angiotensin II on DNA synthesis varies considerably in vascular smooth muscle cells from different Wistar-Kyoto rats.

Abstract

It is well established that angiotensin II induces vascular smooth muscle cell (VSMC) growth but conflicting data exist concerning whether angiotensin II induces cell hypertrophy and/or DNA synthesis from Wistar-Kyoto (WKY) rats. In this study we examined the effect of 10(-7) mol/l angiotensin II on cell protein and DNA synthesis in VSMC (passages 5-30) derived from eight different WKY rats. The mitogenic and hypertrophic effect of angiotensin II was determined by 3H-thymidine incorporation into cell DNA and by total cellular protein measurements. In cells derived from two cell lines, angiotensin II induced a potent mitogenic effect. In cells derived from two other cell lines it induced a weak mitogenic effect. No significant effects on DNA synthesis were observed in cells derived from the four remaining cell lines. Cells from all cell lines reacted to angiotensin II with a 30-40% increase in cell protein. The observed mitogenic effect of angiotensin II was inhibited by losartan, a non-peptide angiotensin II receptor antagonist, proving that the angiotensin II-induced mitogenic effect is directly triggered via the angiotensin II subtype AT1 receptor. The hypertrophic effect of angiotensin II was also illustrated by morphological studies showing that angiotensin II increases the cell size in all cell lines used. Our study shows that angiotensin II not only is a hypertrophic agent, but may also be a potent mitogenic agent for VSMC from WKY rats.