Intimal thickening in arteries is considered a site of predilection for
atherosclerosis. We investigated whether oral application of the
nitric oxide (NO) donors
SPM-5185 [N-nitratopivaloyl-S-(N'-acetylalanyl)-
cysteine ethylester, 10 mg/kg
body weight twice daily (b.i.d.)] and
molsidomine (10 mg/kg
body weight/day) can retard
neointima formation and changes in vascular reactivity induced by a nonocclusive, soft
silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was
sham operated and served as a control.
Drug and placebo (diet without
drug) treatments were initiated 7 days before placement of the collar. At the end of the experiments, two segments were cut from each collared and
sham-treated artery, one for measurement of the cross-sectional area of intima and media and the other for isometric tension recording.
Sham treatment did not result in intimal thickening in either group. In contrast, the intima/media (I/M) ratio was considerably increased after 14 days of collar treatment as a result of
neointima formation. Intimal thickening was significantly inhibited by
SPM-5185 (I/M ratio 0.05 +/- 0.01 vs. 0.11 +/- 0.02, p < 0.05), but not by
molsidomine (0.06 +/- 0.02 vs. 0.08 +/- 0.02, p = 0.49), which is a donor of both NO and
superoxide anions. Neither collar nor NO donor treatment altered the area of the media.
SPM-5185 did not alter the percentage of replicating smooth muscle cells (SMC) in the media after collar treatment, as demonstrated by their immunoreactivity for
proliferating cell nuclear antigen (
PCNA).(ABSTRACT TRUNCATED AT 250 WORDS)