title: Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosis.
abstract: OBJECTIVE
  Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. We hypothesized that those piglets exposed to prolonged iNO react with a modified renal function.
  
  
  METHODS
  Randomized, placebo-controlled exposure to 40 p.p.m. iNO (30 h) in piglets (n = 20). Plasma and urine were sampled during three periods (first and second 12 h periods, and finally a 6 h period). We measured urine volumes, plasma and urine electrolytes (UNa, UK, UCl), plasma creatinine and urea. We calculated creatinine clearance (Ccr), and fractional excretions of sodium and potassium (FENa, FEK) and urinary excretions of electrolytes (UENa, UEK, UECl). Haemodynamic data were recorded and renal tubular apoptosis detected.
  
  
  RESULTS
  For the first 12 h, certain parameters significantly increased in the iNO group (mean +/- SD): UNa (mmol L(-1)), 87.7 (+/-35.0) vs. 39.3 (+/-22.9), UCl (mmol L(-1)) 80.4 (+/-32.8) vs. 48.0 (+/-26.7), FENa (%) 2.1 (+/-0.8) vs. 0.7 (+/-0.5), FEK (%) 31.7 (+/-7.0) vs. 20.7 (+/-12.3), as well as UENa (mmol) 61.0 (+/-21.1) vs. 27.6 (+/-17.9) and UECl (mmol) 57.3 (24.5) vs. 37.6 (29.0). These changes were absent in the second and third periods of the study. Significant differences in percentage of apoptotic cell nuclei in the renal cortex and medulla were found after iNO exposure: 39% vs. 15%.
  
  
  CONCLUSIONS
  Exposure to 40 p.p.m. iNO in healthy anaesthetized piglets has a transient natriuretic effect that disappears after 12 h. We also found evidence of renal tubular apoptosis promotion after 30 h of iNO.
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Wroclaw University of Medicine, Poland. gozdzik@operamail.com
authors.forename: W
authors.initials: W
authors.lastname: Goździk
authors.forename: J
authors.initials: J
authors.lastname: Albert
authors.forename: P
authors.initials: P
authors.lastname: Harbut
authors.forename: S
authors.initials: S
authors.lastname: Zieliński
authors.forename: S
authors.initials: S
authors.lastname: Ryniak
authors.forename: R
authors.initials: R
authors.lastname: Lindwall
authors.forename: P
authors.initials: P
authors.lastname: Dziegiel
authors.forename: M
authors.initials: M
authors.lastname: Podhorska-Okolow
authors.forename: A
authors.initials: A
authors.lastname: Kübler
authors.forename: C
authors.initials: C
authors.lastname: Frostell
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000502:physiology; D002712:Chlorides / Q000652:urine; D004334:Drug Administration Schedule; D007672:Kidney Cortex / Q000502:physiology; D007679:Kidney Medulla / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology*; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D011188:Potassium / Q000652:urine; D013552:Swine; D013997:Time Factors
chemical_list: D002712:Chlorides; D009569:Nitric Oxide; D011188:Potassium