Tranilast, an anti-allergic drug, possesses antagonistic potency to angiotensin II

Citation
D. Jin et al., Tranilast, an anti-allergic drug, possesses antagonistic potency to angiotensin II, EUR J PHARM, 361(2-3), 1998, pp. 199-205
Citations number
30
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
00142999 → ACNP
Volume
361
Issue
2-3
Year of publication
1998
Pages
199 - 205
Database
ISI
SICI code
0014-2999(19981120)361:2-3<199:TAADPA>2.0.ZU;2-A
Abstract
N-(3',4'-dimethoxycinnamoyl) anthranilic acid (tranilast), an effective ant i-allergic drug, has successfully prevented restenosis in patients who have undergone percutaneous transluminal coronary angioplasty. To elucidate the mechanism of tranilast, we investigated its antagonistic effect to angiote nsin II, which plays a pivotal role in the proliferation of vascular smooth muscle cells, using angiotensin II-induced contractions in human gastroepi ploic artery and rabbit aorta. The possible antagonistic effects of other a nti-allergic agents such as 4-( p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-az epin-4-yl)-1(2H)-phthalazinone hydrochloride (azelastine), 9-methyl-3-(1H-t etrazol-5-yl)-4H-pyrido[1,2-a]pyramidin-4-one potassium salt (pemirolast) a nd disodium cromoglycate were also compared. Tranilast dose-depmdently inhi bited the angiotensin II-induced contractions in human and rabbit arteries (IC50 = 3.6 x 10(-5) M and pD(2)' = 3.69, respectively). Pemirolast showed a weak antagonistic effect to angiotensin II, but the effective concentrati on cannot be administered in clinical dosage. Tranilast and pemirolast had no effect on the concentration-contractile response curves for KCI and nore pinephrine. Azelastine inhibited angiotensin II-, KCl- and norepinephrine-i nduced contractions non-specifically, while disodium cromoglycate did not a ffect these contractile responses. Tranilast but not azelastine showed syne rgistic action with 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl] -1H-benzimidazole-7-carboxylic acid (CV-11974) in antagonizing angiotensin II-induced contraction and the inhibitory pattern was similar to that of th e non-peptide angiotensin II AT(1) receptor antagonist CV-11974. These find ings indicate that only tranilast possesses the unique ability to antagoniz e angiotensin II in clinical dosage, which may contribute at least in part to prevention of restenosis after percutaneous transluminal coronary angiop lasty. (C) 1998 Elsevier Science B.V. All rights reserved.