Effect of angiotensin II on the expression of the early growth response gene c-fos and DNA synthesis in human vascular smooth muscle cells

Objectives The aims of this study were to characterize the angiotensin II receptor subtype present on vascular smooth muscle cells from human saphenous vein and to assess the effect of angiotensin II on the expression of the early growth response gene c-fos and on DNA synthesis. Methods and results Using radioligand binding studies, we have defined the angiotensin II receptors present on these cells as being predominantly of the AT(1) subtype. Angiotensin II increased peak intracellular calcium levels by 126+/-16 nmol/l (mean+/-SEM) in 17/49 cultures. Angiotensin II induced c-fos expression in a concentration-dependent manner only in cultures that exhibited an intracellular calcium transient in response to stimulation with angiotensin II, The induction of c-fos was inhibited by the selective AT(1) antagonist losartan in accordance with the binding studies. Angiotensin II stimulated DNA synthesis with a maximal increase of 66.4%+/-20.5% over serum-free levels at 1 nmol/l (mean +/- SEM, n = 6, P < 0.05). DNA synthesis declined with increasing angiotensin II concentration, falling to control values at 1 mu mol/l, suggesting that a growth-inhibitory influence may counterbalance the stimulatory effect that is observed at lower concentrations. Conclusion Vascular smooth muscle cells from human saphenous vein possess predominantly AT(1) receptors and in response to angiotensin II show an induction of c-fos and a modest increase in DNA synthesis.