Vasodilator agents modulate rat glomerular mesangial cell growth and collagen synthesis

Mesangial cell activation and extracellular matrix accumulation are hallmarks of many forms of glomerulonephropathy. We investigated the effect of several agents possessing vasodilating activities on rat mesangial cell growth and collagen synthesis. Using cell counting and a modified MTT assay, it was shown that dipyridamole, pentoxifylline, dicentrine, prazosin and doxazosin all caused a dose-dependent inhibition of serum-stimulated rat mesangial cell proliferation. Platelet-derived growth factor-induced cell proliferation was also inhibited by doxazosin and pentoxifylline. Dipyridamole and pentoxifylline inhibited collagen synthesis in confluent mesangial cells while dicentrine and doxazosin did not. The procollagen alpha 1 (I) mRNA expression was also decreased 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 glomerulopathy associated with mesangial proliferation.