Premium
Nitric oxide synthase distribution and expression with ischemic preconditioning of the rat liver
Author(s) -
Koti Rahul S.,
Tsui Janice C.,
Lobos Edgar,
Yang Wenxuan,
Seifalian Alexander M.,
Davidson Brian R.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3220fje
Subject(s) - enos , nitric oxide , ischemic preconditioning , arginine , nitric oxide synthase , ischemia , nitrite , chemistry , medicine , endocrinology , biochemistry , pharmacology , nitrate , amino acid , organic chemistry
This study was undertaken to identify nitric oxide synthase (NOS) isoforms responsible for the generation of cytoprotective NO during liver ischemic preconditioning (IPC). Sprague‐Dawley rats were subjected to 45 min lobar ischemia followed by 2 h reperfusion. l ‐arginine or Nω‐nitro‐ l ‐arginine methyl ester (L‐NAME) was administered to stimulate or block NO synthesis. Study groups ( n =6) had 1) sham laparotomy, 2) ischemia reperfusion (IR), 3) IPC with 5 min ischemia and 10 min reperfusion before IR, 4) l ‐arginine before IR, or 5) L‐NAME + IPC before IR. Liver function tests, nitrite + nitrate (NO x ) and plasma amino acids were analyzed. The endothelial cell and inducible isoforms of NOS (eNOS and iNOS) were identified using immunohistochemistry and Western blotting. Both IPC and l ‐arginine treatment increased NO x ( P <0.05) and improved serum liver enzymes ( P <0.05) when compared with IR. These effects were prevented by L‐NAME. Hepatic vein NO x was significantly higher than circulating NO x . iNOS expression was absent within the groups. The preconditioned livers were associated with up‐regulation of eNOS expression and also increased l ‐arginine levels. The effects of l ‐arginine administration were similar to those evident following IPC. Thus, cytoprotective NO generation during IPC of the liver was a result of increased eNOS expression and increased l ‐arginine substrate availability.