title: Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS.
abstract: The rupture of cerebral aneurysm (CA) and subsequent subarachnoid hemorrhage can cause fatal results. Recent experimental findings have suggested that the mechanism of CA formation is based on chronic inflammation in arterial walls by hemodynamic force. Endothelial nitric oxide synthase (eNOS) protects arterial walls from vascular inflammation by relieving hemodynamic force through nitric oxide (NO) production. Thus, the expression and protective role of eNOS in CA formation have been investigated in this study. In this study, experimental induced rodent CA models by carotid ligation and systemic hypertension were used. The expression of eNOS was examined in rat CA models and revealed that it was decreased at the site of CA formation. Next, CA was induced in eNOS(-/-) mice to clarify the role of eNOS in CA formation. In eNOS(-/-) mice, the incidence of CA formation was similar to that found in wild-type mice. In CA walls of eNOS(-/-) mice, the expression of neuronal nitric oxide synthase (nNOS) was upregulated compared with that in wild-type mice, suggesting the compensatory effect of nNOS. Hence, eNOS(-/-) nNOS(-/-) mice were generated, underwent CA induction and confirmed that eNOS(-/-) nNOS(-/-) mice exhibited an increased incidence of CA formation accompanied by accelerated macrophage infiltration. These results suggested that the deficiency of eNOS could be compensated by nNOS upregulation in cerebral arteries and that the eNOS and nNOS complementarily had the protective role in CA formation. The results of this study will provide us with new insight about the mechanisms of CA formation and the functional redundancy between eNOS and nNOS in cerebral arteries.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Aoki
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Kataoka
authors.forename: Ryota
authors.initials: R
authors.lastname: Ishibashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nozaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D002339:Carotid Arteries; D018932:Chemokine CCL2 / Q000378:metabolism; D006973:Hypertension / Q000150:complications; D002532:Intracranial Aneurysm / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008026:Ligation; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III