CALCIUM-CHANNEL BLOCKERS INHIBIT HYDROGEN PEROXIDE-INDUCED PROLIFERATION OF CULTURED RAT MESANGIAL CELLS

The present experiments were designed to assess a possible role of H2O 2 in the proliferation of cultured rat mesangial cells, as well as to evaluate the effect of different calcium channel blockers and a platel et-activating factor antagonist on this proliferation. Cultured rat me sangial cells were plated at two densities (10,000 and 25,000 cells/we ll) in 24-well dishes, and proliferation was measured by analyzing [H- 3]thymidine incorporation and by directly counting the cells. Hydrogen peroxide, 100 muM, increased [H-3]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 i t was blocked completely by verapamil and diltiazem, 10 muM, but not b y TMB-8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester] at the same concentration. BN 52021, a competitive antagonist of platele t-activating factor, only slightly blocked the H2O2-dependent prolifer ation. The inhibitory action of the two calcium antagonists tested sta rted at concentrations as low as 1 nM, and inhibited completely the H2 O2 stimulated proliferation at concentrations between 0.1 and 1 muM. T hese results establish that H2O2 is able to induce proliferation of me sangial cells. Although the pathophysiological implications of this fi nding remain to be proven, these data suggest a potential therapeutic action of calcium antagonist in inflammatory conditions such as glomer ulonephritis.