Biomedical Engineering Reference
In-Depth Information
isoprostanes can operate via endothelial cells by releasing endothelin. Isoprostanes
also constrict lymphatic vessels [
1148
].
9.10.8
Hypoxic Vasoconstriction of Pulmonary Arteries
Hypoxic pulmonary vasoconstriction is a localized, acute, adaptive mechanism
that optimizes ventilation-perfusion ratio, as it bypasses blood flow toward highly
ventilated regions of lungs, away from poorly ventilated zones. Hypoxic pulmonary
vasoconstriction is typically biphasic, with a large, transient phase and a sustained,
gradual second stage that are associated with an acute relatively large then stabilized
small Ca
2
+
influx [
1149
]. Hypoxic, transient Ca
2
+
response results from an influx
through voltage-gated Ca
2
+
channels and then release from Ca
2
+
stores. In the
second phase, the effect of low Ca
2
+
influx is enhanced by a RoCK-dependent
Ca
2
+
sensitization. Calcium sensitization of contractile fibers results from inhibition
of myosin light chain phosphatase and subsequent increased phosphorylation of 20-
kDa myosin light chain (MLC20), independently of changes in intracellular Ca
2
+
concentration. Inhibition of MLCP results from phosphorylation of the myosin-
binding regulatory (inhibitory) subunit of protein phosphatase-1 by RoCK kinase.
Among cytosolic protein Tyr kinases of the SRC family, Fyn, Src, and Yes
kinases are highly expressed in pulmonary arteries, where they are involved in
contraction of vascular smooth myocytes. Hypoxia enhances phosphorylation (acti-
vation) of Fyn, Src, and Yes kinases, causes translocation of RoCK from the nucleus
to the cytoplasm, and subsequent phosphorylation of PP1
r12a
and MLC20 [
1149
].
Hypoxic pulmonary vasoconstriction involves the generation in mitochondria of
reactive oxygen species, which stimulate SRC family kinases. Phosphorylation of
PP1
r12a
by RoCK concomitant with a small Ca
2
+
influx greatly enhances MLC20
phosphorylation. On the other hand, PP2 inhibitor of SRC family kinases blocks the
hypoxia-primed Ca
2
+
response in intraparenchymal pulmonary arteries.
In addition, hypoxia activates Src and Fyn kinases in cardiomyocytes. Among
other protein targets, SRC family kinases phosphorylate (activate) focal adhesion
kinases FAK1 and paxillin [
1149
]. Besides, prostanoids cause vascular smooth
muscle contraction partly via RoCK-mediated PP1
r12a
phosphorylation. Kinases of
the SRC family contribute to PGF2
-mediated Ca
2
+
sensitization [
1149
].
α
9.10.9
Hypoxic Vasodilation of Cerebral Arterioles
Functional hyperemia relies on activation neuronal nitric oxide synthase NOS1, in
particular upon glutamate binding to NMDA receptors and increase in intracellular
calcium content.
Adenosine triphosphate is an intra- and extracellular regulator. Red blood
capsules respond to changes in their environment, in particular, by releasing ATP,
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