Biomedical Engineering Reference
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production of secondary NO donors that can inhibit platelet aggregation and support
vasodilation of cerebral arterioles [
1145
]. However, peroxynitrite alters not only
myogenic response of cerebral arteries, but also vasodilation induced by calcitonin
gene-related peptide [
1144
]. Products of peroxynitrite reactions with molecules can
be detected in vascular diseases, ischemia-reperfusion injury, circulatory shock, and
inflammation, among others [
1147
].
9.10.7.5
Isoprostanes
Isoprostanes are unconventional eicosanoids formed from non-enzymatic
peroxidation of membrane fatty acids such as arachidonic acid by free radicals and
other types of reactive oxygen species, without direct action of cyclooxygenases.
187
These inflammatory mediators serve as markers of oxidative stress, in particular
in
.
188
Once
isoprostanes are released into the blood circulation, they are quickly catabolized
and eliminated. Free radical scavengers, such as vitamin-A, -C, and -E,
smokers,
especially
prostaglandin-like
compound
8-iso-PGf2
α
-carotene,
selenium, superoxide dismutase, and catalase, reduce isoprostane levels [
1148
].
In endothelia of microvessels, 8-iso-PGf2
β
upregulates endothelin-1 expression
as well as synthesis of TxA2 and IP
3
, hence increasing cytosolic calcium concen-
tration [
1148
].
Some isoprostanes constrict cerebral microvessels via plasmalemmal receptors
or indirectly via thromboxane liberation from endothelial cells [
1144
]. 8-iso-
PGf2
α
elicits vasoconstriction in the renal vasculature [
1148
]. In human small
pulmonary arteries and veins, among isoprostanes of the E-ring set (8-iso-PGe1
and 8-iso-PGe2) and of the F-ring set (8-iso-PGf1
α
α
and -
β
, 8-iso-PGf2
α
and -
β
,
and 8-iso-PGf3
), 8-iso-PGe2 are the most potent in pulmonary arteries and
have a nearly equivalent efficiency than that to 8-iso-PGf2
α
α
in pulmonary veins.
Isoprostanes 8-iso-PGe1, 8-iso-PGf1
α
, and 8-iso-PGf2
β
) are weakly effective;
8-iso-PGf1
are ineffective [
1148
]. The contraction of vascular
smooth myocytes results from activation of the Rho-RoCK pathway. In addition,
β
and 8-iso-PGf3
α
187
Four classes of F2-isoprostanes can arise from arachidonic acid. In addition, other polyun-
saturated fatty acids targeted by reactive oxygen species produce isoprostanes. Peroxidation of
eicosapentaenoic acid may generate 6 classes of F3-isoprostanes, that of
α
-and
γ
-linolenic
acids to 2 classes of E1- and F1-isoprostanes, and that of docosahexaenoic acid to 8 classes
of D4-isoprostanes and 8 classes of E4-isoprostanes [
1148
]. Cyclooxygenase also contribute
to isoprostane production in vascular smooth myocytes, endothelial cells, platelets, monocytes,
macrophages, and mesangial cells via COx-derived reactive oxygen species [
1148
].
188
The level of 8-iso-PGF2
α
rises in healthy individuals exposed to cigarette smoke, allergen,
ozone, and hyperoxia, as well as in patients with asthma, chronic obstructive pulmonary disease,
interstitial lung disease, cystic fibrosis, acute lung injury such as acute respiratory distress
syndrome and pulmonary hypertension and in patients with ischemia-reperfusion injury, unstable
angina, heart failure, coronary heart disease, stroke, and atherosclerosis [
1148
]. Concentrations of
free and esterified isoprostanes in plasma of smokers remain significantly elevated for weeks after
smoking cessation.
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