title: Endogenous nitric oxide regulates blood vessel growth factors, capillaries in the cortex, and memory retention in Sprague-Dawley rats.
abstract: The effects of nitric oxide (NO) on cerebral capillary angiogenesis and the regulation of pro- and anti-angiogenic factors that affect cerebral capillary angiogenesis, spatial learning, and memory ability are unclear. We assessed the effects of the NO precursor L-arginine (L-ARG) and the NO synthesis inhibitor Nω-nitro-L-arginine methylester (L-NAME) on cortical capillaries and spatial learning and memory abilities. We administered intracerebroventricular injections of L-ARG or L-NAME to rats before they were evaluated in the Morris water maze. We measured the levels of NO synthase activity, pro-angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and the expression of the anti-angiogenic factors angiostatin and endostatin. We also quantitatively investigated parameters of the cortical capillaries using immunohistochemistry and stereological methods. The L-ARG treatment significantly improved rats' spatial learning abilities and increased NOS activity in the cortex. L-NAME disrupted spatial learning. Following the L-ARG treatment, the expression of the pro-angiogenic factors (VEGF and FGF-2) was higher and the expression of anti-angiogenic factors (endostatin) was lower than the vehicle-treated animals. In contrast, the L-NAME treatment reduced the expression of VEGF and increased the expression of endostatin. Based on these results, modulation of the NO content in the brain regulates VEGF, FGF-2, and endostatin expression, as well as capillary parameters in the cortex, which in turn influence spatial learning and memory performance.
authors.affiliation: Department of Rehabilitation Medicine and Physical Therapy, Second Affiliated Hospital, Chongqing Medical University Chongqing, P. R. China.
authors.forename: Sanrong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Yingqiang
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Rehabilitation Medicine and Physical Therapy, Second Affiliated Hospital, Chongqing Medical University Chongqing, P. R. China.
authors.forename: Lehua
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Chao
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Rehabilitation Medicine and Physical Therapy, Second Affiliated Hospital, Chongqing Medical University Chongqing, P. R. China.
authors.forename: Rongzhong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Rehabilitation Medicine and Physical Therapy, Second Affiliated Hospital, Chongqing Medical University Chongqing, P. R. China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiu
authors.affiliation: Department of Histology and Embryology, Chongqing Medical UniversityChongqing, P. R. China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical UniversityChongqing, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
keywords: Nitric oxide; angiogenesis; pro- and anti-angiogenic factors; spatial learning and memory; stereology