Biomedical Engineering Reference
In-Depth Information
3.5.7.4
Nitric Oxide Carrier
Hemoglobin also carries nitric oxide that improves oxygen delivery in the peripheral
tissues and contributes to the control of respiration. Nitric oxide binds reversibly
to a specific cysteine residue (highly conserved Cys93 in all mammals) in globin
β
chain. S-nitrosylated hemoglobin influences NO-mediated regulation of vascular
resistances, blood pressure, and ventilation. Nitric oxide is transported by an anion
exchanger SLC4a1 out of RBCs that then dispense NO activity.
Nitric oxide undergoes oxidative and reductive reactions to produce various
chemical species, such as nitrite (NO
2
), nitrosothiols, nitrosoamines, nitrated lipids,
and iron nitrosyl complexes. It is scavenged by reactions with hemoglobin in RBCs
to form nitrate (NO
3
), methemoglobin (
Fe
3
+
Hb), and ferrous nitrosyl hemoglobin
(
Fe
2
+
Hb
NO
) after the reduction of nitrite by deoxyhemoglobin to NO and reaction of
NO with deoxyhemoglobin (
nitrite-deoxyhemoglobin reaction
)[
145
]:
Fe
3
+
Hb
NO
2
+
H
+
→
OH
−
,
NO
+
+
(3.4)
Fe
3
+
Hb
Fe
2
+
Hb
NO
+
→
.
NO
(3.5)
On the other hand, nitrate formation in RBCs results from the reaction of nitrite with
oxyhemoglobin (
O
2
Hb;
nitrite-oxyhemoglobin reaction
)[
145
]:
4
NO
2
+
H
+
4
NO
3
+
4
Fe
3
+
Hb
O
2
Hb
2
+
+
→
+
O
2
+
2H
2
O
.
(3.6)
In addition, nitrite can bind to methemoglobin to produce a nitrite-bound
methemoglobin intermediate that can interconvert to a ferrous-nitrogen dioxide
species, which reacts with NO to form ferrous hemoglobin and dinitrogen trioxide
(N
2
O
3
)[
145
]:
Fe
3
+
Hb
Fe
3
+
Hb
NO
2
NO
2
+
→
,
(3.7)
Fe
3
+
Hb
NO
2
Fe
2
+
Hb
NO
2
+
Fe
2
+
Hb
←→
NO
→
+
N
2
O
3
,
(3.8)
The overall nitrite-deoxyhemoglobin reaction then becomes [
145
]:
Fe
2
+
Hb
Fe
2
+
Hb
2NO
2
+
H
+
→
OH
−
.
+
+
+
N
2
O
3
(3.9)
Nitrite can quickly enter RBCs (rate constant 0.25 /mn) [
145
]. With a nitrite dose
of 800
mol, erythrocytic uptake rate is approximately 4-fold higher than that in
vitro. Iron nitrosyl hemoglobin is rapidly formed. The overall consumption of fer-
rous nitrosyl hemoglobin is fast in comparison with elimination of methemoglobin
and plasma nitrate (elimination time
∼
40, 105, and 300 mn, respectively).
In pulmonary arteries, hypoxemia normally causes vasoconstriction to match
perfusion to ventilation. Nitric oxide synthases and
S
nitrosoglutathione reductase
in RBCs determine intraerythrocytic content in nitric oxide and nitric oxide-
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