Upregulation of endothelial constitutive NOS: a major role in the increased NO production in cirrhotic rats.
Nitric oxide (NO) is postulated to mediate the peripheral arterial vasodilation in cirrhosis. However, it is not known which isoform of the nitric oxide synthase (NOS) is involved in the increased production of NO. This study was therefore undertaken to examine the expression of the NOS isoforms in arteries of cirrhotic rats compared with controls. Cirrhosis was induced by CCl4, and vessels were harvested for immunoblots using antibodies against inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS). Endothelial cells were used as controls for ecNOS, and vascular smooth muscle cells treated with lipopolysaccharide or septic rats were used for iNOS controls. The results demonstrated an upregulation of ecNOS in both the aortas and mesenteric arteries of cirrhotic compared with control rats. Chronic inhibition of NOS decreased ecNOS in cirrhotic vessels. Although iNOS mRNA was found by reverse transcription-polymerase chain reaction in arteries of cirrhotic rats, iNOS protein was not detectable by immunoblotting compared with septic rats, suggesting a low vascular level of this isoform. In conclusion, the ecNOS seems to play a major role in the increased NO production in cirrhotic rats, whereas the role of iNOS remains elusive.
Martin
P Y
PY
Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
Xu
D L
DL
Niederberger
M
M
Weigert
A
A
Tsai
P
P
St John
J
J
Gines
P
P
Schrier
R W
RW
D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase