Biomedical Engineering Reference
In-Depth Information
Chapter 3
Role of Nitric Oxide in Cardiovascular
Disorders
Introduction
Although one of the simplest biological molecules in nature, nitric oxide (NO) has
found its way into nearly every phase of biology and medicine, ranging from its
role as a critical endogenous regulator of blood flow and thrombosis to a principal
neurotransmitter mediating erectile function as well as a major pathophysiological
mediator of inflammation and host defense. Role of NO in medicine and pharma-
cology is discussed in more detail in a special report on this topic (Jain
2011b
).
These major discoveries have stimulated intense and extensive research into a
vast array of fields including chemistry, molecular biology, and gene therapy. NO
has so many facets that it is uniting many fields of medicine including neurology,
cardiology, and immunology. As a reactive gas, NO functions both as a signaling
molecule in both endothelial and nerve cells, as well as a killer molecule by acti-
vated immune cells.
NO, like other small neutral gases, can diffuse across cell to its site of action.
Because it contains an unpaired electron, it is extremely active. The major mecha-
nism of termination of biological action of NO is its reaction with O
2
to form NO
2
,
which in aqueous solution results in the formation first of N
2
O
3
and then N
2
O
2
−
.
N
2
O
2
−
is then further oxidized by a variety of endogenous oxidants to NO
3
−
, which
is relatively innocuous. Free NO is a transient species with a half-life of only about
5 s. Hence, most studies on NO actions are based on the activity of nitric oxide
synthase (NOS). NO binds to the heme moiety of guanylate cyclase, and causes
greater than 400-fold activation of the enzyme.
Endothelial NO production results in local formation of adducts that may act as
storage forms of NO. Experimental studies indicate that NO photolytically released
in the tissue originates from species with photophysical properties similar to those
reported for low-molecular-weight S-nitrosothiols, as well as from nitrite. The rela-
tive contribution of these potential NO stores to the extent of photorelaxation (abil-
ity to release NO when illuminated with light and subsequently relax vascular
smooth muscle) is consistent with their concentrations detected biochemically in
vascular tissue when their photoactivity was taken into account. These observations
indicate that intravascular nitroso species and nitrite both have the potential to
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