Calcium channel blockers inhibit hydrogen peroxide-induced proliferation of cultured rat mesangial cells.
The present experiments were designed to assess a possible role of H2O2 in the proliferation of cultured rat mesangial cells, as well as to evaluate the effect of different calcium channel blockers and a platelet-activating factor antagonist on this proliferation. Cultured rat mesangial cells were plated at two densities (10,000 and 25,000 cells/well) in 24-well dishes, and proliferation was measured by analyzing [3H]thymidine incorporation and by directly counting the cells. Hydrogen peroxide, 100 microM, increased [3H]thymidine incorporation at the two densities tested (85 and 59%, respectively), as well as the number of cells (53 and 23%, respectively). This effect was dose dependent and it was blocked completely by verapamil and diltiazem, 10 microM, but not by TMB-8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester] at the same concentration. BN 52021, a competitive antagonist of platelet-activating factor, only slightly blocked the H2O2-dependent proliferation. The inhibitory action of the two calcium antagonists tested started at concentrations as low as 1 nM, and inhibited completely the H2O2 stimulated proliferation at concentrations between 0.1 and 1 microM. These results establish that H2O2 is able to induce proliferation of mesangial cells. Although the pathophysiological implications of this finding remain to be proven, these data suggest a potential therapeutic action of calcium antagonist in inflammatory conditions such as glomerulonephritis.
Duque
I
I
Department of Physiology and Pharmacology, Alcalá de Henares University, Madrid, Spain.
Rodriguez Puyol
M
M
Ruiz
P
P
Gonzalez-Rubio
M
M
Diéz Marques
M L
ML
Rodriguez Puyol
D
D
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000493:pharmacokinetics; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D014316:Tritium; D006861:Hydrogen Peroxide; D014700:Verapamil; C045856:ginkgolide B; D013917:Thrombin; D004110:Diltiazem; D013936:Thymidine