Nitric oxide but not prostacyclin mediates poststenotic dilatation (PSD) in rabbit femoral artery

摘要

The pronounced dilatation of vessels distal of a stenosis is a dramatic response of vessel and vascular cell function to hemodynamic forces. The earliest descriptions of poststenotic dilatation (PSD) date back to 1842 but the mechanisms andmediators of the process are still unknown. Over days to months, degenerative changes in the vessel wall include a decrease in smooth muscle cell number density, elastin content, and an increase in collagen, fenestration of the internal elastic lamina,and enhanced collagenase activity.Fluid shear stress enhances endothelial production of nitric oxide (NO) and prostacyclin (PGI{sub}2) and elevates eNOS and C-type natriuretic peptide expression, and suppresses endothelin gene expression in cultured endothelium. Yet, the region distal ofthe stenosis is a site of low pressure and low wall shear stress where recirculation eddies oscillate with the cardiac cycle.Turbulence induced vibration had been hypothesized to cause of PSD. However, Gow et al. have shown that mechanical vibration of rabbit thoracic aorta in vivo does not cause vasodilation. Additionally, Ojha have conducted extensive flow visualization ofmodel stenosed rabbit carotids and found that PSD can occur with stenoses from 50 to 60 % diameter reduction in the carotids where no transition to turbulence is observed in corresponding flow models. In flow models of more severe carotid stenoses of 70 % diameter reduction, a very localized transition to turbulence was identified (6-8 tube diameters downstream) during the early deceleration phase of the cardiac cycle. However, vortex shedding did not correlate with the position of maximal PSD.