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Am J Physiol Gastrointest Liver Physiol 272: G1034-G1040, 1997;
0193-1857/97 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 5 1034-G1040, Copyright © 1997 by American Physiological Society


ARTICLES

Hypothalamic nitric oxide synthase is depressed in cholestatic rats

M. G. Swain, T. Le, A. W. Tigley and P. Beck
Liver Unit, University of Calgary, Alberta, Canada.

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.


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