First 11 pages of thesis. - OPUS - Universität Würzburg

shown that nNOS inhibits leukocyte/endothelial cell interactions in the
cremasteric microcirculation of mice, in the absence of eNOS 161 . In a mouse
carotid artery ligation model, nNOS derived nitric oxide suppresses both
neointimal formation and constrictive vascular remodelling 162 . In the same study
the authors have shown that nNOS exerts an important inhibitory effect on
vasoconstrictor response following balloon injury. Though there was no
expression of nNOS before vascular injury, nNOS was up regulated in the
neointima and medial smooth muscle cells after carotid artery ligation and
balloon injury, suggesting a vasoprotective effect of nNOS in response to injury.
Gene transfer of nNOS in venous bypass grafts resulted in substantial reduction
of adhesion molecule expression and inflammatory cell infiltration in early
venous bypass grafts (3 days after operation) 163 . In late venous bypass grafts
(28 days after operation), nNOS gene transfer resulted in reduction of smooth
muscle cell hyperplasia and reduced vascular superoxide production 163 .
nNOS is detected in endothelial cells and macrophages in both early and
advanced atherosclerotic lesions in humans, while it is absent in normal
vessels 164 . nNOS is also expressed in the carotid artery of spontaneously
hypertensive rats 157 and in the aorta of apoE ko 165 and apoE/iNOS double
knockout (dko) mice 166 . Because nNOS is induced in various vascular
pathologies like atherosclerosis, vascular injury and hypertension, nNOS should
not be considered a “constitutive” enzyme. Rather, nNOS is subject to
expressional regulation in the vascular system, while it is constitutively
expressed in the nervous system 167 . We have recently shown that genetic
deletion of nNOS resulted in accelerated atherosclerosis in apoE ko mice 165 ,
suggesting that nNOS is atheroprotective. We also showed that nNOS improves
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