Hypothalamic nitric oxide synthase is depressed in cholestatic rats

Am J Physiol. 1997 May;272(5 Pt 1):G1034-40. doi: 10.1152/ajpgi.1997.272.5.G1034.


We examined hypothalamic nitric oxide synthase (NOS) levels and release as well as steady-state mRNA levels in rats with cholestasis due to bile duct resection (BDR) and in sham-resected control rats. BDR rats had a significant reduction in hypothalamic NOS-containing neurons in the hypothalamic paraventricular nucleus as determined by NADPH-diaphorase staining, compared with sham-resected controls. In addition, NOS activity, measured indirectly by determining nitrite release from hypothalamic explants, was significantly lower in BDR rats compared with sham-resected animals. Hypothalamic steady-state NOS mRNA levels [brain constitutive NOS (bNOS)] were determined by semiquantitative reverse transcription-polymerase chain reaction and were found to be increased 1.5-fold in BDR rats compared with sham rats. In summary, BDR rats have diminished hypothalamic NOS levels and activity coupled with enhanced steady-state bNOS mRNA levels, suggesting that depressed hypothalamic NOS protein levels are due to posttranscriptional defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cholestasis / enzymology*
  • Enzyme Induction
  • Hypothalamus / enzymology*
  • Male
  • NADPH Dehydrogenase / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitrites / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Staining and Labeling
  • Transcription, Genetic


  • Nitrites
  • RNA, Messenger
  • Nitric Oxide Synthase
  • NADPH Dehydrogenase