Suppression of fibroblast proliferation in vitro and of myointimal hyperplasia in vivo by the triazolopyrimidine, Trapidil.
Platelet derived growth factor (PDGF) is a mitogen capable of stimulating the proliferation of both vascular smooth muscle cells (SMC) and fibroblasts in tissue culture. Recently, it was reported that this in vitro stimulatory effect is significantly reduced by Trapidil, a triazolopyrimidine. We confirm this, and also that similar inhibition occurs in vivo, in balloon catheter deendothelialized aorta of male, Sprague-Dawley rats treated with Trapidil. Two groups of rats, of 8 animals each, were treated daily with oral doses of either 45 mg or 90 mg Trapidil. A third group of 9 control animals were treated identically, but received only the diluent used to dissolve the drug. ADP or collagen-induced platelet aggregation, and endothelial cell regrowth were unaffected by Trapidil administration, but the degree of myointimal hyperplasia was significantly reduced in all animals receiving the drug. Thus, Trapidil seems to possess the selective ability to alter the SMC proliferative response which normally follows deendothelialization.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006965:Hyperplasia / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014192:Trapidil / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D014192:Trapidil