NIFEDIPINE, LOSARTAN AND CAPTOPRIL EFFECTS ON HYPERPLASIA OF VASCULARSMOOTH-MUSCLE FROM REN-2 TRANSGENIC RATS

Vascular smooth muscle cells from hypertensive transgenic rats for the mouse Ren-l gene exhibited radioimmunoassayable angiotensin II and hy perplasia in comparison with cells from Sprague-Dawley rats. However, neither captopril, losartan, saralasin, nor PD123319 (all at 10 mu M) modified DNA synthesis or cell number observed in 4-day growth curves with 10% fetal calf serum. Nifedipine reduced DNA synthesis in both ce ll types, the concentration required being significantly higher in Spr ague-Dawley- (1 mu M) than in transgenic-derived cultures (100 nM). Th e EC50 values were of 2.43 +/- 0.32 and 1.0 +/- 0.17 mu M, respectivel y (P < 0.05). In both cell types, only 10 mu M nifedipine reduced seru m-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-con verting enzyme inhibitors or angiotensin receptor antagonists, but the se cells are more sensitive to the antiproliferative effects of nifedi pine. (C) 1997 Elsevier Science B.V.