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Godofredo Diéguez Castrillo
Figure 2. Schematic representation of the relation of the endothelial release of relaxing and contracting factors in healthy, normal arteries
(left), and unhealthy, diseased arteries (right).
Early changes in endothelial function are indicators of
future cardiovascular morbidity and mortality.
Endothelial cell dysfunction related with aging in healthy
persons is linked to telomere shortening, but it could be
accelerated by risk factors, such as atherosclerosis,
arterial hypertension, smoking, diabetes mellitus, obesity, and laboratory entity that may be accompanied by
and mechanical stress of a high heart rate (26-30). Such
insults accelerate a proatherogenic phenotype (30-32).
The statement “You are only as old as your
endothelium”, attributed to Dr. Rudolf Altschul (1901-
1963), may be right.
Our understanding of the role of the endothelium in
the coronary vasculature under normal and pathological
conditions is very notable (1, 15-18, 20, 30, 31). Due to
its hemodynamic characteristics, the coronary vasculature
may be the prime site for endothelial dysfunction (18)
and displays an unusual gene pattern compared with
other blood vessels, with lower endothelial NO synthase
(eNOS) and higher of ET-1 mRNA expression (32). This
pattern predisposes coronary vasculature to endothelial
dysfunction and atherosclerosis, and coronary arteries are
a main target for the aging and effects of cardiovascular
risk factors. Summarizing, the coronary vasculature is
prone to predominate the effects of ET-1 over those of
NO with aging, cardiovascular risk factors and some
pathological situations.
The first demonstration of endothelial dysfunction in
atherosclerotic coronary arteries using intracoronary
infusion of acetylcholine (Ach) and quantitative coronary
angiography dates back to 1986 (33). This observation
drew attention to the functional manifestations of
atherosclerosis such as exaggerated vasoconstriction as a
consequence of poorly functioning endothelium. Later,
less invasive techniques were developed using mainly the
forearm circulation as a surrogate for coronary arteries
(30, 31, 34, 35).
18 @Real Academia Nacional de Farmacia. Spain
Atherosclerosis, the main cause of acute coronary
syndrome, courses with endothelial dysfunction, and this
dysfunction could play a relevant role in pathophysiology
of myocardial ischemia-reperfusion. And also,
myocardial ischemia-reperfusion by itself is a clinical
damage and dysfunction of coronary vasculature,
particularly of the endothelium (see below). These ideas
support the interest for investigate the functional aspects
of the coronary circulation after myocardial ischemia-
reperfusion in order to know the pathophysiology of this
condition, as well as to design therapeutic strategies to
ameliorate the consequences of acute myocardial
infarction and reperfusion injury, and thus the outcome of
patients with these abnormalities.
In the past decade, many studies have suggested that
the noninvasive assessment of endothelial function may
provide useful information for individual patient risk,
progress, and guidance of therapy.
2.3. Nitric oxide (NO)
In mammals, including humans, nitric oxide (nitrogen
oxide or nitrogen monoxide) is an important cellular
signaling molecule involved in many physiological and
pathological processes (for revision of this issue, see
reference 36).
NO is a gas that has not colour, odour, or taste, with
low solubility in water at room temperature and at
atmospheric pressure. In blood, it reacts predominantly
with molecules that have orbitals with unpaired electrons,
which are typically other free radicals (superoxide ion,
hydroxyl ion) or transition metals like heme iron
(hemoglobin, myoglobin, cytochromes). Reactions of NO
differ between in vitro and in vivo systems. In in vitro
systems, the main degradation product of NO is NO2-
(nitrite), while in vivo the main product is NO3- (nitrate)