Inhibition of angiotensin II and platelet-derived growth factor-induced vascular smooth muscle cell proliferation by calcium entry blockers.
Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 microM did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 microM, while no significant influence was seen with concentrations from 10 nM up to 1 microM. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.
Ko
Y D
YD
Medizinische Universitäts-Poliklinik Bonn.
Sachinidis
A
A
Graack
G H
GH
Appenheimer
M
M
Wieczorek
A J
AJ
Düsing
R
R
Vetter
H
H
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D008790:Metoprolol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D004110:Diltiazem; D008790:Metoprolol; D015773:Enalaprilat; D009543:Nifedipine