Biomedical Engineering Reference
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hemoglobin involved in the construction of hemoglobin-based oxygen carriers is
limited by their increased capacity to produce pulmonary vasoconstriction by NO
scavenging action.
Role of NO in Pathomechanism of Cardiovascular Disorders
Oxidative Stress as a Cause of Cardiovascular Disease
Excessive production and/or inadequate removal of ROS, especially superoxide
anion, have been implicated in the pathogenesis of many cardiovascular diseases,
including atherosclerosis, hypertension, diabetes, and in endothelial dysfunction by
decreasing NO bioactivity. Nanosensing techniques have been developed to monitor
the physiology of NO in the beating heart in vivo. These methods involve the appli-
cation of nanosensors to monitor real-time dynamics of NO production in the heart
as well as the dynamics of oxidative species (oxidative stress) produced in the failing
heart (Malinski
2005
). Results of studies using nanotechnology demonstrated that
African Americans have an inherent imbalance of NO, O
2-
, and ONOO- production in
the endothelium (Jain
2011a
). The overproduction of O
2-
and ONOO- triggers the
release of aggressive radicals and damages cardiac muscle (necrosis), which may
explain why African Americans are at greater risk for developing cardiovascular
diseases, such as hypertension and heart failure, and are more likely to have compli-
cations than European Americans. Potential therapeutic strategies to prevent or ame-
liorate damage to the heart during cardiac events are prevention of O
2-
and
ONOO- production, supplementation of NO (NO donors), and scavenging of O
2-
(antioxidants)
Since the vascular levels of O
2-
are regulated by the superoxide dismutase (SOD)
enzymes, a role of SOD in the cardiovascular disease is of substantial interest.
A major form of SOD in the vessel wall is the extracellular SOD.
Vascular aging may be related to oxidative stress. Age-related morphologic
changes in large resistance vessels include an intima-media thickening, increased
deposition of matrix substances, thus ultimately leading to a reduced compliance.
Vascular aging is mainly characterized by an impaired endothelium-dependent
vasorelaxation. The expression of endothelial nitric oxide synthase (eNOS), pro-
ducing vasodilatatory NO, is markedly upregulated with increasing age. However,
vasorelaxation is impaired as the production of ROS, such as superoxide (O
2-
),
concomitantly increases.
Role of NO in Pathomechanism of Cardiovascular Diseases
Interactions between superoxide and NO underlie many physiologic and pathophys-
iologic processes. Xanthine oxidoreductase (XOR), a prototypic superoxide pro-
ducing enzyme, and nNOS coimmunoprecipitate and colocalize in the sarcoplasmic
reticulum of cardiac myocytes. Deficiency of nNOS (but not eNOS) leads to pro-
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