Biomedical Engineering Reference
In-Depth Information
Endothelial function has also been assessed in pulmonary arteries of
smokers with normal lung function (6). In these subjects, the magnitude
of endothelium-dependent vascular relaxation is intermediate between that
of patients with mild-to-moderate COPD and that of nonsmokers, suggest-
ing that cigarette smoking per se might exert a detrimental effect on
endothelial function of pulmonary arteries (6).
Impairment of endothelial function may be associated to or result
from changes in the expression and release of vasoactive mediators.
Endothelium-derived nitric oxide (NO) is a potent endogenous vasodilator
with antiproliferative properties in the vessel wall. NO is synthesized from
l-arginine by NO synthase, which is expressed constitutively in endothelial
cells (eNOS or type III NOS). Giaid and Saleh (20) showed a significant
reduction of eNOS expression in pulmonary arteries in severe forms of both
primary and secondary pulmonary hypertension (including 5 patients with
COPD out of 24), thereby suggesting that downregulation of NO might con-
tribute to the development of pulmonary hypertension. Reduced expression
of eNOS has also been shown in pulmonary arteries of smokers without or
with only minimal airflow obstruction (21). More recent data demonstrate
that eNOS expression in pulmonary arteries is reduced in patients with
different degrees of COPD severity, being the patients with the greatest
severity those with the most reduced expression of eNOS (22).
Prostacyclin is the principal arachidonic acid metabolite of endothelial
cells, produced by the action of prostacyclin synthase (PGI
2
-S). It is a
powerful vasodilator and inhibits cell growth (23). Tuder et al. (24) demon-
strated loss of expression of PGI
2
-S in endothelial cells of pulmonary
arteries of different size in patients with PPH and in associated forms of pul-
monary arterial hypertension. At present, there is no information about the
expression and activity of PGI
2
-S in pulmonary arteries of COPD patients.
However, in a hypoxic model of pulmonary hypertension in piglets, Fike
et al. (25) showed reduced production of prostacyclin in pulmonary arteries.
Endothelin-1 (ET-1) is a potent vasoconstrictor released by endothelial
cells that also exert a mitogenic effect on arterial smooth muscle cells. Part
of the activity of ET-1 on smooth muscle cells is mediated via an increase in
reactive oxygen species production (26). Since oxidative stress is increased in
COPD, it is possible that ET-1 might play a role in the pathogenesis of pul-
monary vascular changes in this disease. Giaid et al. (27) showed that the
expression of ET-1 in pulmonary arteries was increased in both primary
and secondary forms of pulmonary hypertension (including 2 patients with
COPD out of 28). Studies conducted in smokers with normal lung function,
patients with mild-to-moderate COPD, and patients with severe emphy-
sema, have failed to show differences in the expression of ET-1 in pulmon-
ary arteries when compared with nonsmokers (21,22). Although, this could
be due to the fact that patients evaluated in these series did not have
pulmonary hypertension. Furthermore, studies performed in pulmonary
