Levles of malondialdehyde are described as a marker of oxidative stress.
10. Cox, M. J.; Sood, H. S.; Hunt, M. J.; Chandler, D.;
Henegar, J. R.; Aru, G. M.; Tyagi, S. C. JOURNAL NAME- Am J Physiol Heart Circ Physiol VOL. 282 2002 Apr PP.
H1197-205 DOCUMENT TYPE- Journal Article JOURNAL CODE- 100901228 ISSN- 0363-6135 CORPORATE AUTHOR- Department
of Physiology and Biophysics, School of Medicine, University of Mississippi Medical Center, Jackson,
Mississippi 39216, USA. PUBLICATION COUNTRY- United States LANGUAGE- English The hypothesis is that chronic
increases in left ventricular ( LV ) load induce oxidative stress and latent matrix
metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide
(NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed
in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was
administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V
fistula, 2) A-V fistula + Nic, 3) sham operated, 4) sham + Nic, and 5) control (unoperated); n = 6 rats/group.
After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed,
and LV tissue homogeneates were prepared. A-V fistula caused an
increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of
malondialdehyde ( MDA ; a marker of oxidative stress) was 6.60 +/- 0.23 ng/mg protein and NO was 6.87 +/- 1.21
nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 +/- 2.5 nmol/l
and decreased MDA to 3.54 +/- 0.34 ng/mg protein (P = 0.005). Zymographic levels of MMP-2 were increased, as
were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of
oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of
metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic
by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula
rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac
rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation.
Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress
and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and
decreased endocardial endothelial function in chronic LV volume overload.
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