Effects of treatment with FK409, a nitric oxide donor, on collar-induced intimal thickening and vascular reactivity

Intimal thickening in arteries is considered a site of predilection for ath erosclerosis. In a rabbit model of early atherosclerosis, a silastic collar was placed around the carotid artery, which resulted in the formation of i ntimal 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 thic kening as well as accompanying reactivity changes in rabbit carotid artery. The intimal thickening was significantly inhibited by FK409. The collar tr eatment increased the pD(2) value of 5-hydroxytryptamine (5-HT) whereas it decreased those of phenylephrine and acetylcholine and did not significantl y alter that of nitroglycerine. Maximal contractile force development in re sponse to potassium chloride (KCl), 5-HT and phenylephrine was decreased in collared arteries. The collar did not alter the maximal relaxant effects o f acetylcholine and nitroglycerine. Despite the significant reduction of in timal thickening, FK409 treatment did not affect these collar-induced modif ications in vascular reactivity. (C) 1999 Elsevier Science B.V. All rights reserved.