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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/32265

    標題: B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats
    作者: Yeh, Jwu-Lai
    Wu, Jiunn-Ren
    Wu, Bin-Nan
    Yang, Sheau-Fang
    Dai, Zen-Kong
    Liou, Shu-Fen
    Hsu, Jong-Hau
    貢獻者: Department of Pharmacology and Graduate Institute of Medicine, College of Medicine
    Department of Medical Research, Kaohsiung Medical University Hospital
    Kaohsiung Med Univ Hosp, Dept Med Res
    Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources
    Kaohsiung Med Univ Hosp, Dept Pediat
    Kaohsiung Med Univ, Coll Med, Fac Med, Dept Pediat
    I Shou Univ, E Da Hosp, Dept Pediat
    Kaohsiung Med Univ Hosp, Dept Pathol
    Chia Nan Univ Pharm & Sci, Dept Pharm
    關鍵字: Smooth-Muscle-Cells
    日期: 2018-09-28
    上傳時間: 2019-11-15 15:47:23 (UTC+8)
    摘要: The physiologic process of postnatal ductus arteriosus (DA) closure consists of vasoconstriction followed by vascular remodeling. We have recently reported that B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling effects in pulmonary vasculature. However, its effects on DA have not been elucidated. We investigated whether BNP can prevent DA closure, and if so, the underlying mechanisms. Using in vivo studies, we examined effects of BNP (10 mg/kg, ip at birth) on DA closure in neonatal rats within 4 h after birth. We found that in control rats, the DA spontaneously closed at 4 h with a decreased DA diameter, enhanced intimal thickening, and luminal occlusion. BNP prevented DA closure at 4 h with a preserved DA diameter, attenuated intimal thickening, and preserved lumina! patency. Ex vivo, BNP attenuated oxygen-induced vasoconstriction of isolated DA rings of newborn rats. These vasodilating effects were blunted by Rp-8-Br-PET-cGMPS, a cGMP inhibitor. In vitro, BNP inhibited angiotensin II (Ang II)-induced proliferation and migration of DA smooth muscle cells (DASMCs). BNP inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production and calcium overload in DASMCs. Finally, BNP inhibited Ang II-induced ERK1/2 activation. These in vitro effects were antagonized by Rp-8-Br-PET-cGMPS. In conclusion, BNP prevents postnatal DA closure by both vasodilation and anti-remodeling through the cGMP pathway. The mechanisms underlying anti-remodeling effects include anti-poliferation and anti-migration, with attenuation of mitochondrial ROS production and intracellular calcium and ERK1/2 signaling. Therefore, the BNP/cGMP pathway can be a promising therapeutic target for clinical management of DA patency.
    link: http://dx.doi.org/10.1042/CS20180201
    關聯: Plos One, v.132, n.18, pp.2045-2058
    Appears in Collections:[藥學系(所)] 期刊論文

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