Neuronal nitric oxide synthase, nNOS, regulates renal hemodynamics in the postnatal developing piglet

Pediatr Res. 2012 Feb;71(2):144-9. doi: 10.1038/pr.2011.23. Epub 2011 Dec 21.


Introduction: Nitric oxide (NO) vasodilation critically modulates renal hemodynamics in the neonate compared with the adult. Based on the postnatal expression pattern of renal neuronal nitric oxide synthase (nNOS), the hypothesis was that nNOS is the major NOS isoform regulating renal hemodynamics in the immature, but not mature, kidney.

Results: NOS inhibitors did not alter mean arterial pressure (MAP) in either group. Intrarenal S-methyl-L-thiocitrulline (L-SMTC) in newborns significantly reduced renal blood flow (RBF) 38 ± 4%, glomerular filtration rate (GFR) 42 ± 6%, and increased renal vascular resistance (RVR) 37 ± 7%, whereas intrarenal L-nitro-arginine methyl ester (L-NAME) affected RBF, GFR, and RVR equivalent to L-SMTC treatment. When L-NAME was administered after L-SMTC treatment, newborn renal hemodynamic changes were not further altered from what was observed when L-SMTC was administered alone. In contrast, in the adult, only intrarenal L-NAME, and not L-SMTC, affected renal hemodynamic responses.

Discussion: In conclusion, these studies demonstrate that nNOS is an important regulator of renal hemodynamics in the newborn kidney, but not in the adult.

Methods: Experiments compared renal hemodynamic responses with intrarenal infusion of L-NAME, an inhibitor of all NOS isoforms, with the selective nNOS inhibitor L-SMTC in the newborn piglet and the adult pig.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Blood Pressure
  • Citrulline / administration & dosage
  • Citrulline / analogs & derivatives
  • Enzyme Inhibitors / administration & dosage
  • Glomerular Filtration Rate
  • Hemodynamics* / drug effects
  • Infusions, Intra-Arterial
  • Kidney / blood supply*
  • Kidney / drug effects
  • Kidney / enzymology*
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism*
  • Renal Artery / drug effects
  • Renal Artery / enzymology*
  • Renal Circulation* / drug effects
  • Swine
  • Thiourea / administration & dosage
  • Thiourea / analogs & derivatives
  • Vascular Resistance


  • Enzyme Inhibitors
  • Citrulline
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Thiourea
  • S-methylthiocitrulline
  • NG-Nitroarginine Methyl Ester