Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosis.
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.
Goździk
W
W
Department of Anaesthesiology and Intensive Therapy, Wroclaw University of Medicine, Poland. gozdzik@operamail.com
Albert
J
J
Harbut
P
P
Zieliński
S
S
Ryniak
S
S
Lindwall
R
R
Dziegiel
P
P
Podhorska-Okolow
M
M
Kübler
A
A
Frostell
C
C
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
D002712:Chlorides; D009569:Nitric Oxide; D011188:Potassium