Upregulation of the endothelial constitutive nos: a major role in
the increased no production in cirrhotic rats.
Martin, Pierre-Yves, Ding Li Xu, Michel Niederberger, Andre Weigert,
Phoebe Tsai, Judy St John, Pere Gines, Robert W. Schrier.
Department of Medicine, Division of Renal Diseases and
Hypertension, University Colorado School of Medicine. Denver, 80262
CO
APStracts 2:0173F, 1995.
Nitric oxide is postulated to mediate the peripheral arterial
vasodilation in cirrhosis. However, it is not known which isoform of
the nitric oxide synthase 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 as compared to
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 as compared to control rats. Chronic
inhibition of NOS decreased ecNOS in cirrhotic vessels. Although iNOS
mRNA was found by RT PCR in arteries of cirrhotic rats, iNOS protein
was not detectable by immunoblotting as compared to 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.
Received 26 April 1995; accepted in final form 27 September1995.
APS Manuscript Number F139-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95