Liver, Pancreas, and Biliary TractContribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct–ligated rats☆,☆☆,★
Section snippets
Reagents and enzymes
DNA synthase, RNA superscript synthase, and polymerase chain reaction (PCR) buffer were purchased from GIBCO BRL, Life Technologies (Gaithersburg, MD). Agarose was obtained from ICN Biomedicals (Aurora, OH), sodium nitrite from BDH (Toronto, ON), and L-NAME and its inactive enantiomer nitro-D-arginine-methyl ester (D-NAME) from Bachem (Torrance, CA). Other reagents were purchased from Sigma Chemical Co. (St. Louis, MO), Bio-Rad (Hercules, CA), or Fisher Scientific (Fairlawn, NJ) and were the
Cytokine levels
TNF-α levels in cardiac homogenates showed a significant increase in the BDL cirrhotic rats compared with those of sham-operated controls (Table 2). Serum IL-1β level was increased in BDL cirrhotic rats compared with that in sham-operated controls (Table 2).
Ventricular NOS2 and NOS3 mRNA and protein expression
A representative NOS2 mRNA RT-PCR Polaroid is shown in Figure 1.
Discussion
In the past few years, some evidence has suggested that NO production is increased in the vasculature in cirrhosis5, 6 (and see Bomzon and Blendis27 for review). However, whether this is predominantly caused by NOS2 stimulated by cytokinemia or NOS3 secondary to the hyperdynamic circulation and shear stress remains unclear. Our data using the nonspecific NOS2 and NOS3 inhibitor L-NAME in the isolated papillary muscle strongly support the results of Van Obbergh et al.16 who found that treatment
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Address requests for reprints to: Samuel S. Lee, M.D., 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1, Canada. e-mail: [email protected]; fax: (403) 270-0995.
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Supported by a research operating grant from the Medical Research Council of Canada. Dr. Lee is a Scholar of the Alberta Heritage Foundation for Medical Research.
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Drs. Liu and Ma contributed equally to this work.