title: Peritoneal dialysis impairs nitric oxide homeostasis and may predispose infants with low systolic blood pressure to cerebral ischemia.
abstract: Infants on chronic peritoneal dialysis (PD) have an increased risk of developing neurological morbidities; however, the underlying biological mechanisms are poorly understood. In this clinical study, we investigated whether PD-mediated impairment of nitric oxide (NO) bioavailability and signaling, in patients with persistently low systolic blood pressure (SBP), can explain the occurrence of cerebral ischemia.
  
  
  
  Repeated blood pressure measurements, serial neuroimaging studies, and investigations of systemic nitrate and nitrite levels, as well as NO signaling, were performed in ten pediatric patients on PD. We consistently observed the loss of both inorganic nitrate (-17 ± 3%, P < 0.05) and nitrite (-34 ± 4%, P < 0.05) during PD, which may result in impairment of the nitrate-nitrite-NO pathway. Indeed, PD was associated with significant reduction of cyclic guanosine monophosphate levels (-59.4 ± 15%, P < 0.05). This reduction in NO signaling was partly prevented by using a commercially available PD solution supplemented with l-arginine. Although PD compromised nitrate-nitrite-NO signaling in all cases, only infants with persistently low SBP developed ischemic cerebral complications.
  
  
  
  Our data suggests that PD impairs NO homeostasis and predisposes infants with persistently low SBP to cerebral ischemia. These findings improve current understanding of the pathogenesis of infantile cerebral ischemia induced by PD and may lead to the new treatment strategies to reduce neurological morbidities.
authors.affiliation: Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address: mattias.carlstrom@ki.se.
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
authors.affiliation: Dept. Radiology, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cananau
authors.affiliation: Dept. of Medical Biochemistry and Biophysics, Div. of Physiological Chemistry 2, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Checa
authors.affiliation: Dept. of Clinical Science, Intervention and Technology, Div. of Pediatrics, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Wide
authors.affiliation: Dept. of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sartz
authors.affiliation: Dept. Radiology, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svensson
authors.affiliation: Dept. of Medical Biochemistry and Biophysics, Div. of Physiological Chemistry 2, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Wheelock
authors.affiliation: Dept. of Pediatrics, The Queen Silvia Children's Hospital, Göteborg, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Westphal
authors.affiliation: Dept. of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Zivile
authors.initials: Z
authors.lastname: Békássy
authors.affiliation: Dept. of Renal Medicine, Karolinska University Hospital, Stockholm, Huddinge, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.affiliation: Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Dept. of Pediatrics, The Queen Silvia Children's Hospital, Göteborg, Sweden.
authors.forename: Sverker
authors.initials: S
authors.lastname: Hansson
authors.affiliation: Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
authors.affiliation: Dept. of Clinical Science, Intervention and Technology, Div. of Pediatrics, Karolinska University Hospital, Huddinge, Sweden. Electronic address: rafael.krmar@ki.se.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: Krmar
mesh_terms: D001120:Arginine / Q000008:administration & dosage; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010530:Peritoneal Dialysis / Q000009:adverse effects*
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP
keywords: Blood pressure; Cerebral ischemia; Chronic kidney disease (CKD); Dialysis; Nitrate; Nitric oxide; Nitric oxide synthase (NOS); Nitrite; cGMP