HYDRALAZINE INHIBITS HUMAN PERITONEAL MESOTHELIAL CELL-PROLIFERATION AND COLLAGEN-SYNTHESIS

The integrity of the mesothelial layer is essential for both defence a nd solute transport in continuous ambulatory peritoneal dialysis (CAPD ), The human peritoneal mesothelial cell (HPMC) culture has been shown to be a very useful tool to study the peritoneal mesothelial stem cel l behaviour. We investigated whether hydralazine, an antihypertensive agent Frequently used, might affect HPMC growth and collagen synthesis . HPMCs were cultured from specimens of human omentum by enzymatic dis aggregation of omentum. HPMC growth was evaluated by modified methylte trazolium (MTT) assay. Cell viability was confirmed by trypan blue exc lusion and lactate dehydrogenase assay. Collagen synthesis was measure d by H-3-proline incorporation into pepsin-resistant, salt-precipitate d collagen. Intracellular cAMP levels were measured by enzyme immunoas say. The procollagen alpha 1 (I) mRNA expression was evaluated by Nort hern blot analysis. Hydralazine inhibited serum-stimulated HPMC growth in a dose-dependent manner. The maximal inhibition was 93% at a conce ntration of 100 mu g/ml. Hydralazine inhibited collagen synthesis in c onfluent mesothelial cells (47% inhibition at a concentration of 100 m u g/ml). The procollagen alpha 1 (I) mRNA expression was also decrease d by hydralazine (about 50% decrease at 100 mu g/ml). These effects ma y be due to the phosphodiesterase inhibition property of hydralazine t o increase intracellular cAMP levels. These data suggest that the use of hydralazine in CAPD patients may affect peritoneal membrane functio n and integrity.