HYPOTHALAMIC NITRIC-OXIDE SYNTHASE IS DEPRESSED IN CHOLESTATIC RATS

We examined hypothalamic nitric oxide synthase (NOS) levels and releas e 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-diapho rase staining, compared with sham-resected controls. In addition, NOS activity, measured indirectly by determining nitrite release from hypo thalamic explants, was significantly lower in BDR rats compared with s ham-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 ha ve diminished hypothalamic NOS levels and activity coupled with enhanc ed steady-state bNOS mRNA levels, suggesting that depressed hypothalam ic NOS protein levels are due to posttranscriptional defects.