Nifedipine, losartan and captopril effects on hyperplasia of vascular smooth muscle from Ren-2 transgenic rats.
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.
Peiró
C
C
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Angulo
J
J
Regadera
J
J
Llergo
J L
JL
Sánchez-Ferrer
A
A
Rodríguez-Mañas
L
L
Sánchez-Ferrer
C F
CF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D006965:Hyperplasia / Q000188:drug therapy / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D002216:Captopril; D009543:Nifedipine; D019808:Losartan