The aim of this study was to evaluate the effect of anti-hypertensive drugs, nifedipine, furosemide, and captopril, on DNA synthesis and proliferation of cultured rat glomerular mesangical and aortic smooth muscle cells induced by fetal calf serum(20% in mesangial cells and 10% in smooth muscle cells). Glomerular mesangial and aortic smooth muscle cells from Sprague-Dawley rats were cultured and seeded in multi-well plates. After confluency and serum restriction(48 hours in mesangial cells and 72 hours in smooth muscle cells), the cells were exposed to fetal calf serum with or without anti-hypertensive drugs at increasing concentration between 10^(-8) -10^(-4)M. DNA synthesis was assessed by ³H-thymidine uptake and proliferation by cell numbers using hemocytometer. The results were as follows:
1) Nifedipine at the concentration of 10^(-5)M and 5×10^(-4)M inhibited serum-induced DNA synthesis significantly by 40.9% and 78.9% in mesangial cells(p<0.05), and by 50.8% and 86.6% in smooth muscle cells(p><0.05), respectively. The results of cell numbers paralleled those of ³H-thymidine uptake.
2) Serum-induced DNA synthesis of mesangial and smooth muscle cells were reduced by 23.5% and 32.6%, respectively, at the highest dose of furosemide(10^(-4M) without statistial significance.
3) Neither hydrochlorothiazide nor captopril exhibited any anti-proliferative effect on mesangial and smooth muscle cells throughout the entire doses.
In conclusion, among the various anti-hypertensive drugs, nifedipine appears to be beneficial in view of a direct inhibitory effect on DNA synthesis and proliferation of mesangial and smooth muscle cells besides of anti-hyertensive effect.
|