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Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein‐stenosed rats after lipopolysaccharide administration
Author(s) -
Heller Jörg,
Sogni Philippe,
Tazi Khalid A.,
Chagneau Carine,
Poirel Odile,
Moreau Richard,
Lebrec Didier
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300301
Subject(s) - phenylephrine , medicine , endocrinology , aorta , endothelium , lipopolysaccharide , umbilical vein , enos , nitric oxide synthase , in vitro , nitric oxide , chemistry , blood pressure , biochemistry
Abstract Hyporeactivity to vasoconstrictors in aortae from portal vein‐stenosed rats is associated with an increased activity of endothelial NO synthase (NOS3). In contrast, during sepsis, which is common in cirrhosis, vascular hyporeactivity is associated with an induction of inducible NOS2. The aim of this study was to investigate the in vitro reactivity to phenylephrine and the regulation of NOS2 and NOS3 in aortae from portal vein‐stenosed rats after lipopolysaccharide (LPS) administration. Aortic vascular reactivity for phenylephrine, aortic NOS activity, and NOS2 and NOS3 protein expression were determined 5 hours after intravenous LPS or saline administration. Moreover, aortic NOS activity was measured after 5‐hour in vitro incubation in LPS. LPS induced a significantly smaller decrease in aortic tension in portal vein‐stenosed than in sham‐operated rats. Under baseline conditions, aortic NOS activity and NOS3 protein expression were higher in portal vein‐stenosed than in sham‐operated rats, and NOS2 protein expression was not detected in aortae from either group. After LPS administration, NOS activity and NOS2 protein expression increased significantly less in portal vein‐stenosed than in sham‐operated rat aortae. Similar results were obtained after in vitro incubation with LPS. Endothelium removal or NOS3 inhibition with the calmodulin inhibitor, W7, increased NOS activity in the aortae of portal vein‐stenosed rats after LPS incubation. In conclusion, in aortae of portal vein‐stenosed rats exposed to LPS, no further decrease in aortic reactivity to phenylephrine was observed, and the induction of NOS2 was down‐regulated. Endothelium removal or calmodulin inhibition inhibits NOS3 overactivity and leads to normalized NOS2 activation after LPS in aortae from portal vein‐stenosed rats.