Pharmacologic agents inhibit rat mesangial cell proliferation and collagen synthesis.
Prevention of the development of end-stage renal disease is one of the most promising areas of research in nephrology. Because mesangial cell proliferation and extracellular matrix accumulation have been regarded as antecedents of glomerulosclerosis, agents that can inhibit mesangial cell proliferation may have a potential to retard the progression of renal diseases. Therefore, we investigated several clinically available agents that might affect mesangial cell proliferation and collagen synthesis in male Sprague-Dawley rats. Cell proliferation was measured by the tetrazolium dye uptake method. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. Our results showed that hydralazine (82% inhibition at 10 micrograms/mL), ticlopidine (61% inhibition at 30 micrograms/mL), aminophylline (66% inhibition at 200 micrograms/mL), and nicametate (91% inhibition at 1 mg/mL) inhibited serum-stimulated rat mesangial cell (RMC) growth in a dose-dependent manner. Ticlopidine (43% inhibition at 30 mg/mL), aminophylline (52% inhibition at 200 mg/mL), and nicametate (35% inhibition at 1 mg/mL) inhibited collagen synthesis in confluent RMCs. Aminophylline may act through increasing intracellular cAMP levels (9.7 +/- 0.7 pmol/mg protein at 200 micrograms/mL of aminophylline vs 4.2 +/- 0.6 pmol/mg protein at control). These data suggest that aminophylline, ticlopidine, hydralazine, and nicametate can inhibit RMC proliferation and collagen synthesis.
Fang
C C
CC
Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yen
C J
CJ
Shyu
R S
RS
Wu
M S
MS
Tsai
T J
TJ
Hsieh
B S
BS
D000628:Aminophylline / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000494:pharmacology
D002317:Cardiovascular Agents; D009539:Nicotinic Acids; D006830:Hydralazine; D000628:Aminophylline; D003094:Collagen; C005392:nicametate; D013988:Ticlopidine