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Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia
P. Babál1,3, O. Pechánová2, I. Bernátová2 and S. Stvrtina3
1Department of Pathology, University of South Alabama, Mobile AL, USA, 21nstitute of Normal and Pathological Physiology, Slovak Academy of Sciences and 2Department of Pathology, Comenius University, Bratislava, Slovakia
Offprint requests to: Dr. Pavel Babal, M.D., Department of Pathology, University of South Alabama, 2451 Fillingim Street, Mobile, AL 36617, USA
Summary. Pathophysiological effects of nitric oxide
(NO)-deficient hypertension are much better known than
are the potential morphological changes. Hearts and
main arteries were studied in 15 week old male Wistar
rats administered NG-nitro-L-arginine methyl ester (LNAME)
for 4 weeks. A dose of 40 mg/kglday increased
systolic arterial pressure by 30%, while heart rate
decreased by 20%. Heart/body weight ratios were not
significantly changed. Total cardiac RNA and DNA
content and [14C]leucine incorporation into myocardial
protein were, however, increased by 15%, 228% and
97%, respectively. Light microscopy of hearts showed
subendocardial areas of necrosis along with different
stages of healing. Morphometric evaluation demonstrated
significant increase in myocardial fibrosis. Serum
lactate dehydrogenase increased by 91 %. Proliferation
cell nuclear antigen (PCNA) immunohistochemistry
indicated positive cells in areas of postischemic repair.
Chronic inhibition of NO synthase (NOS) resulted in
periarterial fibrosis and hyperplasia of the media in
coronary arteries and aorta. RNA and DNA content, and
[14C]leucine incorporation into protein of aorta
increased by 255%, 95% and 49%, respectively. PCNA
staining showed numerous positive nuclei in the media
of coronary arteries and the aorta. It is concluded that
inhibition of NOS leads to systemic hypertension with
focal myocardial fibrosis reflecting reparative responses
associated to ischemic injury. This sequence of
alterations involves impaired arterial relaxation, and
uncontrolled vascular medial proliferation attributed to
the absence of smooth muscle cell proliferation
inhibition by NO. Histol Histopathol 12, 623-629 (1997)
Key words: Nitric oxide (NO), L-NAME, Myocardial
fibrosis, Ischemia, Arterial hyperplasia, Proliferation cell
nuclear antigen (PCNA), Smooth muscle cells
DOI: 10.14670/HH-12.623
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