Tranilast antagonizes angiotensin II and inhibits its biological effects in vascular smooth muscle cells.

Recent studies have been reported indicating that angiotensin II may potentiate neointimal formation. In the present study, we examined the antagonistic effect of tranilast on angiotensin II. Losartan was used as the reference compound. First, tranilast inhibited the angiotensin II-induced contraction of rabbit aortic strips in a noncompetitive manner (pD'(2) = 3.7), whereas it had little effect on the contraction induced by noradrenaline or endothelin-l. Second, tranilast inhibited the binding of (125)I-labeled angiotensin II to angiotensin AT1 receptors in rat liver membranes with an IC(50) value of 289 mu M. Finally, functional antagonism of tranilast (100 and 300 mu M) was demonstrated by its blockade of angiotensin II (10(-8)M)-induced (45)Ca(2+) -efflux from human vascular smooth muscle cells (VSMC). However, tranilast (30-300 mu M) exerted no influence on PDGF-induced formation of inositol triphosphates which cause an increase in [Ca(2+)]i in human VSMC. The antagonistic activity of tranilast towards angiotensin II may be involved in part in preventing restenosis after percutaneous transluminal coronary angioplasty (PTCA).