Biomedical Engineering Reference
In-Depth Information
Support and perfusion media used in flow chambers can bring substances that can
interfere with the cell response to investigated stimuli. Consequently, experimental
testing and result interpretation must be carefully handled.
9.10.3
Nitric Oxide
Nitric oxide (Vol. 4 - Chap. 10. Other Major Signaling Mediators) is a vasodilator
that inhibits vasoconstrictor influence, such as that of angiotensin-2 as well as
sympathetic vasoconstriction. Acetylcholine and muscarinic agonists stimulate NO
release from endothelial cells [
1102
]. Nitric oxide can also be released from the en-
dothelium by activated
2-adrenoceptors and aggregating platelets that particularly
release serotonin and leukotrienes [
1103
]. On the other hand, superoxide (O
2
)and
oxyhemoglobin (HbO
2
) sequester nitric oxide.
α
9.10.3.1
Nitric Oxide and Vascular Cells
Nitric oxide impedes the adhesion of platelets and leukocytes to the vascular
endothelium. It also precludes the proliferation of vascular endothelial and smooth
muscle cells.
Nitric oxide binds to and activates guanylate cyclase that produce cyclic
guanosine monophosphate from guanosine triphosphate. Messenger cGMP
activates PKG kinase that subsequently inhibits calcium influx into smooth
myocytes and decreases Ca
2
+
-calmodulin stimulation of myosin light chain kinase,
thereby decaying smooth muscle tone in the vascular wall.
In endothelial cells, nitric oxide can prevent Ca
2
+
entry and lower intracellular
Ca
2
+
concentration, as nitric oxide exerts a negative feedback. Nitric oxide can
augment calcium uptake into intracellular stores by sarco(endo)plamic reticulum
calcium ATPase to avoid detrimental effects on cell functioning [
1104
]. In aged
cells, reduced phosphorylation of its active site (Ser1177) uncouples NOS3 enzyme.
Tissular hypoxia yields vasodilation in various vessel types. Endothelial cells act
as local sensors for the regulation of O
2
supply, increasing
Ca
2
+
]
i
and releasing
[
nitric oxide and prostacyclin in response to hypoxia [
1105
].
9.10.3.2
Nitric Oxide Production
Nitric oxide is produced by endothelial and smooth muscle cells as well as car-
diomyocytes, among other cell types. The continuous production of nitric oxide is
fostered by multiple stimuli, such as adenosine di- and triphosphate, acetylcholine,
bradykinin, histamine, insulin, and substance P.
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