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Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus

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Abstract

The relative potency and interrelationship between vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in premature infants receiving indomethacin and ibuprofen for therapy of patent ductus arteriosus. Excretion rates of AVP, ET-1 and sodium were measured in premature infants with RDS receiving indomethacin or ibuprofen. Forty-four RDS premature infants (<34-week gestation) with PDA received either ibuprofen (n=22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or 3 doses at 12-h intervals of indomethacin (n=24), 0.2 mg/kg, infused continuously over a period of 15 min. Urinary ET-1, AVP and sodium excretion were measured before and after treatment. Indomethacin treatment caused a significant decrease in urinary ET-1 and AVP excretion (UET-1/Ucr 0.14±0.01 vs. 0.10±0.05 fenton/mmol; P<0.05; 24.42±6.18 vs. 12.63±3.06 pg/mmol; P<0.05, respectively), along with a significant reduction in urinary sodium (92.1±36.1 vs. 64.8±35.6 mmol/l; P<0.01), fractional excretion of sodium (6.8±37.1 vs. 4.5±37.1%; P<0.01) and urinary osmolality (276.2±103.9 vs. 226.4±60.3 mOsmol/kg; P<0.05). Ibuprofen treatment caused a significant decrease in urinary AVP (UAVP/Ucr 24.5±3.4 vs. 16.3±2.04 pg/mmol; P<0.01), along with a significant decrease in urinary sodium (78.0±8.4 vs. 57.0±8.0 mmol/l; P<0.05) and in fractional excretion of sodium (7.5±1.3 vs. 3.9±3.0%; P<0.05), while it did not modify urinary ET-1 excretion. The association of renal ET-1 and AVP activity with sodium excretion in premature infants treated with indomethacin and ibuprofen supports the hypothesis that these factors may play a role in the physiologic changes in sodium excretion.

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References

  1. Endo A, Shimada M, Ayusawa M, Minato M, Takada M, Takahashi S, Harada K, Masaoka N, Sato K (1996) Nitric oxide and endothelin 1 during postnatal life. Biol Neonate 70:15–20

    PubMed  Google Scholar 

  2. Brater DC (1999) Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med 107:65S–70S

    Article  Google Scholar 

  3. Whelton A (2000) Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther 7:63–74

    PubMed  Google Scholar 

  4. Chou S-Y, Dahhan A, Porush IG (1990) Renal actions of endothelin: Interaction with prostacyclin. Am J Physiol 259:645–652

    Google Scholar 

  5. Chou S-Y, Porush IG (1995) Renal action of endothelin-1 and endothelin-3: Interaction with the prostaglandin system and nitric oxide. Am J Kidney Dis 26:116–123

    PubMed  Google Scholar 

  6. Cowley AW, Merrill DC, Smith MJ, Skelton NM (1988) Role of vasopressin in regulation of sodium excretion. Am J Med Sci 295:308–313

    PubMed  Google Scholar 

  7. Miller WL, Redfield MM, Burnett JC (1989) Integrated cardiac, renal and endocrine actions of endothelin. J Clin Invest 83:317–320

    PubMed  Google Scholar 

  8. Leppaluoto J, Ruskoaho H (1992) Endothelin peptides: biological activities, cellular signalling and clinical significance. Ann Med 24:153–161

    PubMed  Google Scholar 

  9. Kohan DE (1991) Endothelin synthesis by rabbit renal tubule cells. Am J Physiol 261:221–226

    Google Scholar 

  10. Wilkes BM, Susin M, Mento PF, Macica CM, Girardi EP, Boss E, Nord EP (1991) Localization of endothelin-like immunoreactivity in rat kidney. Am J Physiol 260:913–920

    Google Scholar 

  11. Zeidel ML, Brady MR, Kone BC, Gullans SR, Brenner BM (1989) Endothelin, a peptide inhibitor of Na+-K+ ATPase in intact renal tubular epithelial cells. Am J Physiol 257:1101–1107

    Google Scholar 

  12. Nadler SP, Zimpelmann JA, Hebert RL (1992) Endothelin inhibits vasopressin stimulated water permeability in rat terminal inner medullary collecting duct. J Clin Invest 90:1458–1466

    PubMed  Google Scholar 

  13. Sulyok E, Ertl T, Adamovits K, Hovanyovszky S, Rascher W (1993) Urinary endothelin excretion in the neonate: influence of maturity and perinatal pathology. Pediatr Nephrol 7:881–885

    Article  PubMed  Google Scholar 

  14. Tsukahara H, Sekine K, Miura M, Todoroki Y, Ohshima Y, Hiraoka M, Hosokawa K, Kotsuji F, Mayumi M (2002) Vasoactive and natriuretic mediators in umbilical cord blood: a report of our observation and review of the literature. Early Hum Dev 69:57–64

    Article  PubMed  Google Scholar 

  15. Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia OS (2002) Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomized controlled trial. Eur J Pediatr 161:202–207

    Article  PubMed  Google Scholar 

  16. Aranda JV, Varvarigou A, Beharry K, Bansal R, Bardin C, Modanlou H, Papageorgiou A, Chemtob S (1997) Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr 86:289–293

    PubMed  Google Scholar 

  17. Johnson GL, Breart GL, Gewitz MH, Brenner JI, Lang P, Dooley KJ, Ellison RC (1983) Echocardiographic characteristics of premature infants with patent ductus arteriosus. Pediatrics 72:864–871

    PubMed  Google Scholar 

  18. Hercule HC, Oyekan O (2000) Role of NO and cytochrome P-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats. Am J Reg Integr Comp Physiol 279:2132–2141

    Google Scholar 

  19. Harris RC (2002) Cyclooxygenase-2 inhibition and renal physiology. Am J Cardiol 89:10–17

    Article  Google Scholar 

  20. Guignard JP (2002) The adverse renal effect of prostaglandin-synthesis inhibitors in the newborn rabbit. Semin Perinatol 26:398–405

    PubMed  Google Scholar 

  21. Clive DM, Stoff JS (1984) Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 310:563–572

    PubMed  Google Scholar 

  22. Brooks DP, Share L, Crofton JT (1986) Role of brain prostaglandins in the control of vasopressin secretion in the conscious rat. Endocrinology 118:1716–1722

    PubMed  Google Scholar 

  23. Walker MP, Moore TR, Brace RA (1994) Indomethacin and arginin vasopressin interaction in the fetal kidney: a mechanism of oliguria. Am J Obstet Gynecol 171:1234–1241

    PubMed  Google Scholar 

  24. Kompanowska-Jezierska E, Emmeluth C, Grove L, Christensen P, Sadowski J, Bie P (1998) Mechanism of vasopressin natriuresis in the dog: role of vasopressin receptors and prostaglandins. Am J Physiol 274:1619–1625

    Google Scholar 

  25. Modesti PA, Cecioni I, Migliorini A, Naldoni A, Costoli A, Vanni S, Serneri GG (1998) Increased renal endothelin formation is associated with sodium retention and increased free water clearance. Am J Physiol 275:1070–1077

    Google Scholar 

  26. Goto K (2001) Basic and therapeutic relevance of endothelin-mediated regulation. Biol Pharm Bull 24:1219–1230

    Article  PubMed  Google Scholar 

  27. Dobyns EL, Eells P, Griebel JL, Abman SH (1999) Elevated plasma endothelin-1 and cytokine levels in children with severe acute respiratory distress syndrome. J Pediatr 135:246–249

    PubMed  Google Scholar 

  28. Bhat R, John E, Chari G, Shankararao R, Fornell L, Gulati A, Vidiyasagar D (1995) Renal actions of endothelin-1 in newborn piglets: dose-effect relation and the effects of receptor antagonist (BQ-123) and cyclooxygenase inhibitor (indomethacin). J Lab Clin Med 126:458–469

    PubMed  Google Scholar 

  29. Munger KA, Takahashi K, Ebert J, Badr KF (1990) Role of cyclooxygenase products in mediating renal responses to endothelin. Kidney Int 37:375

    Google Scholar 

  30. Rascher W, Gyodi G, Worgall S, Sulyok E (1994) Effect of sodium chloride supplementation on urinary endothelin-1 excretion in premature infants. J Pediatr125:793–797

    Google Scholar 

  31. Lievano G, Nguyen L, Radhakrishnan J, Fornell L, Joshi A, John EG (1998) Significance of fractional excretion of sodium and endothelin levels in the early diagnosis of renal failure in septic neonatal piglets. J Pediatr Surg 33:1480–1482

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Padua University School of Medicine, Via Giustiniani 3, 35128, Padua, Italy

    Vincenzo Zanardo, Stefania Vedovato, Paola Lago & Daniele Trevisanuto

  2. Institute of Laboratory Medicine, Padua University School of Medicine, Padua, Italy

    Flaviano Favaro, Diego Faggian & Mario Plebani

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  1. Vincenzo Zanardo
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  2. Stefania Vedovato
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  3. Paola Lago
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  4. Daniele Trevisanuto
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  5. Flaviano Favaro
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  6. Diego Faggian
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  7. Mario Plebani
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Correspondence to Vincenzo Zanardo.

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Zanardo, V., Vedovato, S., Lago, P. et al. Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus. Pediatr Nephrol 20, 1552–1556 (2005). https://doi.org/10.1007/s00467-005-2022-6

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  • DOI: https://doi.org/10.1007/s00467-005-2022-6

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