Effects of pemirolast and tranilast on intimal thickening after arterial injury in the rat.
We previously reported that tranilast, an antiallergic agent, reduced intimal thickening after endothelial injury in rats. In this study, to verify whether or not antiallergic agents inhibit intimal thickening, we investigated the effect of pemirolast on intimal thickening after endothelial injury and compared its effect with that of tranilast. Administration of two antiallergic agents, pemirolast (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2 days before endothelial injury and continued until the animals were killed. Endothelial injury in the rat femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. To evaluate intimal hyperplasia, we measured the cross-sectional area of the intima 21 days after endothelial damage. Pemirolast at doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/- 0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth-muscle cells, we investigated the effects of antiallergic agents on migration by using a modified Boyden chamber assay and on proliferation by using the bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a concentration-dependent manner both migration and proliferation of smooth muscle cells stimulated by platelet-derived growth factor. These results suggest that antiallergic agents directly inhibit migration of smooth-muscle cells to the intima from the media and proliferation in the intima, and that pemirolast has more potent antihyperplastic action than does tranilast. Antiallergic agents may be effective in preventing restenosis after coronary angioplasty.
Miyazawa
N
N
Department of Pharmacology, Hamamatsu University School of Medicine, Handa-cho, Japan.
Umemura
K
K
Kondo
K
K
Nakashima
M
M
D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001158:Arteries / Q000293:injuries* / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology*; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D051381:Rats; D017539:Tunica Intima / Q000473:pathology; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
D000963:Antimetabolites; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D011725:Pyridines; D011744:Pyrimidinones; D062367:ortho-Aminobenzoates; C055139:pemirolast; D001973:Bromodeoxyuridine; C012293:tranilast