VASODILATOR AGENTS MODULATE RAT GLOMERULAR MESANGIAL CELL-GROWTH AND COLLAGEN-SYNTHESIS

Mesangial cell activation and extracellular matrix accumulation are ha llmarks of many forms of glomerulonephropathy. We investigated the eff ect of several agents possessing vasodilating activities on rat mesang ial cell growth and collagen synthesis. Using cell counting and a modi fied MTT assay, it was shown that dipyridamole, pentoxifylline, dicent rine, prazosin and doxazosin all caused a dose-dependent inhibition of serum-stimulated rat mesangial cell proliferation. Platelet-derived g rowth factor-induced cell proliferation was also inhibited by doxazosi n and pentoxifylline. Dipyridamole and pentoxifylline inhibited collag en synthesis in confluent mesangial cells while dicentrine and doxazos in did not. The procollagen alpha 1 (I) mRNA expression was also decre ased by dipyridamole and pentoxifylline. These results suggested that, in addition to dipyridamole, pentoxifylline and alpha(1)-adrenoceptor blockers may have a potential to delay the progression of chronic glo merulopathy associated with mesangial proliferation.