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| 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
Labedipinedilol-A
Proliferation
Hypertension
Mechanisms
Pathway
Aldosterone
Activation
Migration
Aorta |
| 日期: | 2018-09-28 |
| 上傳時間: | 2019-11-15 15:47:23 (UTC+8) |
| 出版者: | PORTLAND PRESS LTD |
| 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 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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