{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:07:54Z","timestamp":1771650474442,"version":"3.50.1"},"reference-count":32,"publisher":"Portland Press Ltd.","issue":"18","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,9,28]]},"abstract":"<jats:p>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 luminal 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.<\/jats:p>","DOI":"10.1042\/cs20180201","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T01:02:42Z","timestamp":1537059762000},"page":"2045-2058","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats"],"prefix":"10.1042","volume":"132","author":[{"given":"Jwu-Lai","family":"Yeh","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"},{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiunn-Ren","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"},{"name":"Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin-Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheau-Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zen-Kong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"},{"name":"Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Fen","family":"Liou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Hau","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"},{"name":"Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"2021113010592402400_B1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0031-6997(24)01348-6","article-title":"The pharmacology of the ductus arteriosus","volume":"50","author":"Smith","year":"1998","journal-title":"Pharmacol. 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