title: Decreased serum osmolality promotes ductus arteriosus constriction.
abstract: OBJECTIVE
  At birth, dynamic changes occur in serum components and haemodynamics, such as closure of the ductus arteriosus (DA). A previous study demonstrated that, in full-term human neonates, serum osmolality decreased transiently after birth, but recovered over the next few days. However, the significance of this transient decrease in osmolality has never been addressed. The objective of the present study was to examine the role of changes in serum osmolality after birth in DA closure.
  
  
  RESULTS
  We found that rats exhibited a similar transient hypoosmolality after birth. Hypotonic stimulation induced constriction of DA rings and increased Ca(2+) transient in DA smooth muscle cells, but not in the aorta. The hypoosmotic sensor transient receptor potential melastatin 3 (TRPM3) was highly expressed in the rat DA, and TRPM3 silencing abolished the Ca(2+) response to hypoosmolality. Pregnenolone sulfate stimulation of TRPM3 induced rat DA constriction ex vivo and in vivo. Furthermore, hypertonic fluid injection impaired rat DA closure. In humans, neonatal serum hypoosmolality was observed in relatively mature preterm infants (≥28 weeks). In extremely preterm infants (<28 weeks), however, this hypoosmolality was absent. Instead, a rapid increase in osmolality occurred thereafter. Such an increase was greater, in particular, among patent DA (PDA) patients.
  
  
  CONCLUSIONS
  A transient decrease in serum osmolality may promote DA closure during the first few days of life. Adjusting serum osmolality to proper levels might help to prevent the onset of PDA, improving the therapeutic outcome in extremely preterm infants.
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan utako@yokohama-cu.ac.jp yishikaw@med.yokohama-cu.ac.jp.
authors.forename: Utako
authors.initials: U
authors.lastname: Yokoyama
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University Graduate School of Advanced Science and Engineering, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Kumagaya
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ishiwata
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Yanai
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okumura
authors.affiliation: Department of Physiology, Aichi Medical University, Nagakute, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University Graduate School of Advanced Science and Engineering, Tokyo, Japan Department of Cell Physiology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
authors.affiliation: Department of Cardiovascular Surgery, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Asou
authors.affiliation: Department of Surgery, Yokohama City University, Yokohama, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Iwasaki
authors.affiliation: Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishimaki
authors.affiliation: Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Seki
authors.affiliation: Department of Pediatrics, Yokohama City University, Yokohama, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan utako@yokohama-cu.ac.jp yishikaw@med.yokohama-cu.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D002478:Cells, Cultured; D004373:Ductus Arteriosus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004374:Ductus Arteriosus, Patent / Q000097:blood* / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D005865:Gestational Age; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009994:Osmolar Concentration; D064587:Osmoregulation; D011247:Pregnancy; D034622:RNA Interference; D017208:Rats, Wistar; D044967:Serum / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D050053:TRPM Cation Channels; C533867:TRPM3 protein, rat; D014662:Vasoconstrictor Agents
keywords: Biology; Developmental; Osmolality; Paediatrics; Patent ductus arteriosus; TRP channel