Hypothalamic nitric oxide synthase is depressed in cholestatic rats.
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.
Swain
M G
MG
Liver Unit, University of Calgary, Alberta, Canada.
Le
T
T
Tigley
A W
AW
Beck
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D002779:Cholestasis / Q000201:enzymology*; D004790:Enzyme Induction; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014158:Transcription, Genetic
D009573:Nitrites; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase