Nifedipine, losartan and captopril effects on hyperplasia of vascular smooth muscle from Ren-2 transgenic rats.

ABSTRACT

Vascular smooth muscle cells from hypertensive transgenic rats for the mouse Ren-2 gene exhibited radioimmunoassayable angiotensin II and hyperplasia in comparison with cells from Sprague-Dawley rats. However, neither captopril, losartan, saralasin, nor PD123319 (all at 10 microM) modified DNA synthesis or cell number observed in 4-day growth curves with 10% fetal calf serum. Nifedipine reduced DNA synthesis in both cell types, the concentration required being significantly higher in Sprague-Dawley- (1 microM) than in transgenic-derived cultures (100 nM). The EC50 values were of 2.43 +/- 0.32 and 1.0 +/- 0.17 microM, respectively (P < 0.05). In both cell types, only 10 microM nifedipine reduced serum-induced cell proliferation, but inhibition percentage was higher in transgenic-derived cultures. In conclusion, hyperplasia of transgenic-derived vascular smooth muscle cells is not blocked by angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, but these cells are more sensitive to the antiproliferative effects of nifedipine.