Intimal thickening in arteries is considered a site of predilection for atherosclerosis. In a rabbit model of early atherosclerosis, a silastic collar was placed around the carotid artery, which resulted in the formation of intimal thickening. We investigated whether the oral application of FK409 ((+)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide, 10 mg kg(-1) day(-1), p.o.), a nitric oxide donor, inhibited the collar-induced intimal thickening as well as accompanying reactivity changes in rabbit carotid artery. The intimal thickening was significantly inhibited by FK409. The collar treatment increased the pD(2) value of 5-hydroxytryptamine (5-HT) whereas it decreased those of phenylephrine and acetylcholine and did not significantly alter that of nitroglycerine. Maximal contractile force development in response to potassium chloride (KCl), 5-HT and phenylephrine was decreased in collared arteries. The collar did not alter the maximal relaxant effects of acetylcholine and nitroglycerine. Despite the significant reduction of intimal thickening, FK409 treatment did not affect these collar-induced modifications in vascular reactivity. (C) 1999 Elsevier Science B.V. All rights reserved.