Protective effects of calcium channel blockers on hydrogen peroxide induced increases in endothelial permeability.
OBJECTIVE
The aim was to examine the effects of calcium channel blockers on the permeability of endothelial cells and to determine whether these agents could protect against increases in endothelial permeability induced by hydrogen peroxide (H2O2).


METHODS
Endothelial cells were cultured on collagen coated micropore filters. When they were confluent on the filter, albumin transfer and electrical resistance across the endothelial monolayers were measured.


METHODS
Endothelial cells were obtained from human umbilical veins. The cells at the 2nd to 4th passage were used for the experiments.


RESULTS
Nilvadipine (10(-8) M) suppressed endothelial albumin transfer by 37.2% (p less than 0.01) and enhanced electrical resistance by 25.8% (p less than 0.01), whereas nicardipine (10(-7) M), diltiazem (10(-7) M), and verapamil (10(-7) M) had no significant effect on either variable without the addition of H2O2. H2O2(0.2 mM) increased albumin transfer by 164% (p less than 0.01) and reduced electrical resistance by 67% (p less than 0.01) across endothelial monolayers without endothelial cell lysis. Nilvadipine (10(-8) M) and nicardipine (10(-7) M) inhibited the (0.2 mM) H2O2 induced increases in endothelial albumin transfer and decreases in electrical resistance more strongly than diltiazem and verapamil, although all of these agents significantly reduced such injury.


CONCLUSIONS
Nilvadipine is a potent inhibitor of endothelial permeability and of hydrogen peroxide induced increases in permeability.
Yamada
Y
Y
Nagoya University School of Medicine, Japan.
Yokota
M
M
Furumichi
T
T
Furui
H
H
Yamauchi
K
K
Saito
H
H
D000418:Albumins / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000418:Albumins; D002121:Calcium Channel Blockers; C035100:nilvadipine; D006861:Hydrogen Peroxide; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine