Biomedical Engineering Reference
In-Depth Information
9.5.5.5
Gasotransmitters
Endogenous gaseous diffusible messengers, or gasotransmitters, include carbon
monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H
2
S), in addition to
several reactive oxygen species, that act as intra- and intercellular regulators.
In addition, feedbacks exist among different gasotransmitters that enable the
regulation of the action of a given gas by others gaseous mediators [
910
].
Carbon Monoxide
Carbon monoxide (CO) is a stable, lipid-soluble gas, produced by heme oxygenase
(HO) with iron and biliverdin, using NADPH from heme degradation [
911
]
(Vol. 4-Chap. 10. Other Major Signaling Mediators). Although CO can bind to
heme-containing proteins for transient storage and later release, the predominant
source is de novo synthesis. It then diffuses according to the local partial pressure
gradient. Carbon monoxide binds to the ferrous iron of heme and, then, influences
the activity of all heme proteins.
Carbon monoxide not only causes vasodilation, but also supports action of
vasodilators and attenuates that of vasoconstrictors such as platelet-activating factor.
Endothelial nitric oxide and prostacyclin (PGi2) cooperate with the HO-CO axis to
regulate the blood circulation. On the other hand, H
2
S can inhibit heme oxygenase-2
in endothelial cells [
911
].
Nitric Oxide
Nitric oxide (NO) a highly diffusible gas that runs very rapidly from its site of
synthesis. However, NO is a labile vasodilator with a limited half-life of NO
(
[1 s]); its effect is thus localized close to the site of release. This free radical is
highly reactive with other chemical species, notably oxygen, superoxide, and iron-
containing hemes that act as NO scavengers. Nitric oxide is able to serve as an auto-,
para-, and endocrine signal (Vol. 4 - Chap. 10. Other Major Signaling Mediators).
Nitric oxide can complex with all transition metals, the so-called metal nitrosyls.
Nitric oxide interacts with metalloproteins, especially those that contain hemes, and
with thiols. Nitric oxide can act in the form of free radical (NO or NO
)oras
chemical species, such as nitrosyl (NO
+
) or nitroxyl (NO
−
) ions or
S
nitrosothiols
(SNO). Hemes either transform NO into nitrate or promote its transformation into
S
nitrosothiols.
Additional sources of nitric oxide than nitric oxide synthases arise from the
cycling of nitrate, nitrite, and nitric oxide. Several pathways modulate the NO
3
-
NO
2
-NO cycling, such as oxidation or reduction by hemoglobin, myoglobin,
neuroglobin, xanthine oxidoreductase (XOR), nitric oxide synthase, carbonic an-
hydrase, cytochrome-C oxidase, cyclooxygenase, microsomal cytochrome-P450,
O
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