BIGDELY M R, HAJIZADEH S, SHAHRAZ S. PULMONARY VASCULAR MUSCLE PROLIFERATION AS A RESULT OF PROTEIN AND mRNA-eNOS ALTERATIONS IN A RAT MODEL OF CHF. Med J Islam Repub Iran 2002; 16 (2) :101-105
URL:
http://mjiri.iums.ac.ir/article-1-760-en.html
From the Department of Microbiology, Islamic Azad University, Zanjan
Abstract: (4653 Views)
Endothelial Nitric Oxide Synthase (eNOS) produces nitric oxide (NO)
from L-arginine and is important for the maintenance of cardiovascular homeostasis.
Congestive heart failure (CHF) generally results in increased pulmonary
blood flow and if untreated leads to pulmonary hypertension and end
stage heart failure. We therefore hypothesized that increased pulmonary flow
without changes in pressure would result in hypertrophy of the media (middle
layer of vascular wall). NO produced by the lung is regulated by systemic
blood flow and in turn adjusts smooth muscle proliferation via altered expression
of eNOS. To study this hypothesis, we created an artificial aortocaval
shunt in order to increase pulmonary flow for 7 weeks. The shunt resulted in
a significant thickening of the media. eNOS Western and Northern blot analysis
demonstrated no significant alterations of eNOS protein and mRNA levels
in the large-shunted group but in the small shunted one in comparison with
sham. We suggested that NO in low concentrations (about > 10µM) caused
weak hypertrophy of the media in the small-shunted group and in high concentrations
(about> 50µM) caused S-nitrosylation of eNOS protein and deamination
of eNOS mRNA and the regulatory genes in the nucleus thus the media
of the vascular wall was significantly thickened in the large-shunted group.
In higher concentrations, NO induces apoptosis and decreased cell viability.