Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 1, Number 3, November 2005
Contents
The Emergent Cardiovascular Risk Factors and Organ Damage
in Arterial Hypertension Pp.189
Cristiana Catena, Roberta Lapenna, Sara Baroselli, Marileda
Novello,Elisa Nadalini, Gian Luca Colussi, Giorgio Soardo,
Alessandro Cavarape and Leonardo A. Sechi
[Abstract]
Reactive Oxygen Species, Nitric Oxide and Hypertensive
Endothelial Dysfunction Pp.201
Ulvi Bayraktutan
[Abstract]
Left Ventricular Hypertrophy Beyond Hemodynamics:
Genetic, Metabolic and Hormonal Factors Pp.217
Alberto Palazzuoli, Giovanna Giannotti, Stefano Capobianco
and Ranuccio Nuti
[Abstract]
Brachial-Ankle Pulse Wave Velocity as a Novel Measure
of Arterial Stiffness:Present Evidences and Perspectives Pp.223
Masanori Munakata, Tohru Nunokawa, Jun Tayama, Kaoru Yoshinaga
and Takayoshi Toyota
[Abstract]
Epoxyeicosatrienoic Acids as a Therapeutic Target
for Nephropathy Associated with Diabetes and Hypertension
Pp.235
Jeffrey J. Olearczyk and John D. Imig
[Abstract]
Cardiotonic Steroids: Novel Mechanisms of Na+i-Mediated
and – Independent Signaling Involved in the Regulation
of Gene Expression, Proliferation and Cell Death
Pp.243
Sergei N. Orlov, Olga A. Akimova and Pavel Hamet
[Abstract]
Diagnosis of Surgically-Treatable forms of Primary
Aldosteronism Pp.259
Paolo Mulatero, Alberto Milan, Franco Rabbia, Corrado
Garrone,Denis Rossato and Franco Veglio
[Abstract]
SDH Genes: From Glomic Tumours to Pheochromocytomas
Pp.267
Alexander Persu and Miikka Vikkula
[Abstract]
A Systematic Approach to Hypertensive Urgencies
and Emergencies Pp.275
Seth R. Bender, John D. Filippone, Sabine Heitz and John
D. Bisognano
[Abstract]
Abstracts
[Back to top]
The Emergent Cardiovascular Risk Factors and Organ
Damage in Arterial Hypertension
Cristiana Catena, Roberta Lapenna, Sara Baroselli, Marileda
Novello, Elisa Nadalini, Gian Luca Colussi, Giorgio Soardo,
Alessandro Cavarape, Leonardo A. Sechi
Correction of cardiovascular risk factors is a mainstay
of the treatment of hypertensive patients that have developed
or might develop target organ damage. In addition to traditional
risk factors, such as smoking, diabetes, obesity, and dyslipidemia,
clinical research has identified additional conditions that
put patients at a greater risk of developing cardiovascular
disease and that might achieve particular relevance in the
hypertensive state. Over the last decades, effective intervention
in the treatment of traditional risk factors has reduced remarkably
cardiovascular morbidity and mortality, but the incidence
of coronary artery disease, stroke, and renal failure remains
unacceptably high. Emerging cardiovascular risk factors are
likely to contribute substantially to this picture and it
could be anticipated that their contribution will become increasingly
evident in the future. Physicians involved in the field of
hypertension and dealing with problems concerning cardiovascular
prevention should be aware of these new risk factors, give
them an appropriate consideration, and correct them whenever
possible. This review will consider the literature supporting
the role of lipoprotein(a), homocysteine, and fibrinogen as
contributors to cardiovascular risk in the general population
and, more specifically, to the development and progression
of target organ damage in hypertensive patients. The impact
of early impairment of renal function on these factors will
be analyzed in relation to the progression of renal disease
as found in patients with hypertensive nephrosclerosis.
[Back to top]
Reactive Oxygen Species, Nitric Oxide and Hypertensive
Endothelial Dysfunction
Ulvi Bayraktutan
Endothelial dysfunction, a hallmark of many vascular diseases
such as diabetes mellitus, atherosclerosis and essential hypertension,
refers to significant impairment of a majority of endothelial
activities e.g. modulation of vasomotor tone and inhibition
of smooth muscle cell proliferation and/or migration. Several
factors including increased synthesis of vasoconstrictor agents
through the cyclooxygenase pathway and dysregulation of the
gene encoding endothelial type of nitric oxide synthase in
endothelium have been proposed to account for this defect
in hypertensive subjects. However, a growing body of evidence
has recently implicated diminished bio-availability of nitric
oxide (NO), the most important endogenous vasodilator agent,
due to excessive synthesis or reduced destruction of reactive
oxygen species (ROS) in the pathogenesis of hypertensive endothelial
dysfunction. Hence, this review aims to summarize the mechanisms
by which vascular cells produce NO and ROS, to highlight the
molecular mechanisms underlying the pathogenesis of hypertensive
endothelial dysfunction with particular reference to interactions
between ROS and NO, and finally to discuss the reversal of
hypertensive endothelial dysfunction.
[Back to top]
Left Ventricular Hypertrophy Beyond Hemodynamics:
Genetic, Metabolic and Hormonal Factors
Alberto Palazzuoli, Giovanna Giannotti, Stefano Capobianco
and Ranuccio Nuti
Left Ventricular Hypertrophy (LVH) is a risk factor for
major cardiovascular diseases as stroke, myocardial infarction
and sudden death, and is sustained by several hemodynamic
and non-hemodynamic mechanisms. A wide spectrum of alterations
in left ventricular hypertrophy geometric pattern can take
the form of normal left ventricle, concentric left ventricular
remodeling, concentric left ventricular hypertrophy, eccentric
LVH.
Hemodyn amicand anatomic characteristics of LVH are represented
by the alteration of coronary blood flow, endothelial dysfunction,
extracellular collagen deposition and ventricular fibrosis.
However, other biological phenomena such as genotype, gender,
body size, environmental factors can influence left ventricular
mass. The most important mechanism remains the activation
of neurohormonal systems (first of all, renin-angiotensin
system, secondarily catecolamines, insulin and leptin). Actual
data cannot explain some LVH characteristics (LVH pattern
development, LVH regression), so several open questions remain
to be clarified through further investigations.
[Back to top]
Brachial-Ankle Pulse Wave Velocity as a Novel Measure
of Arterial Stiffness: Present Evidences and Perspectives
Masanori Munakata, Tohru Nunokawa, Jun Tayama, Kaoru Yoshinaga
and Takayoshi Toyota
Atherosclerotic cardiovascular disease is a leading cause
of death in most developed countries. Cardiovascular risk
factors such as hypertension, diabetes, and dyslipidemia initiate
structural and functional abnormalities in the arterial wall,
leading to the development of atherosclerosis. Atherosclerosis
is characterized by the stiffening and/or thickening of the
arterial wall. Aortic pulse wave velocity as evaluated by
carotid and femoral arterial waves is the most established
measure for arterial stiffness. Recently, a new arterial stiffness
measure using brachial and tibial arterial waves has been
developed. The measurement of the brachial-ankle wave velocity
is fully automatic, needs no skill and is reproducible. Age
and blood pressure are robust independent predictors for the
brachial-ankle pulse wave velocity. Recent studies have shown
that higher brachial ankle pulse wave velocity is associated
with more advanced atherosclerotic changes of the arterial
wall not only in the clinical patients but also in subclinical
individuals. Thus, brachial-ankle pulse wave velocity may
be a useful measure of vascular damage, which predisposes
individuals to cardiovascular events. A multicenter trial
examining the prognostic significance of the brachial-ankle
pulse wave velocity is presently in progress.
[Back to top]
Epoxyeicosatrienoic Acids as a Therapeutic Target
for Nephropathy Associated with Diabetes and Hypertension
Jeffrey J. Olearczyk and John D. Imig
Nephropathy developing from hypertension and/or non-insulin
dependent diabetes mellitus (NIDDM) is becoming increasingly
prevalent in the world population. Although there is a significant
amount of research being conducted in this area, the etiologies
of nephropathy are not known. It has been proposed that hemodynamic
and metabolic alterations in the kidney contribute to the
development and progression of nephropathy. More interesting
however, is the identification of an inflammatory component
to nephropathy that is characterized by increased expression
of nuclear transcription factors, increased cytokine expression
and interstitial cell infiltration. Cytochrome P450 epoxygenase
metabolites have recently been reported to regulate sodium
excretion as well as renal blood flow and blood pressure.
In addition, the epoxyeicosatrienoic acids (EETs) have been
identified as anti-inflammatory mediators. We propose that
EETs can prevent the development and progression of nephropathy
associated with NIDDM and hypertension, by inhibiting the
expression of pro-inflammatory genes.
[Back to top]
Cardiotonic Steroids: Novel Mechanisms of Na+i-Mediated
and -Independent Signaling Involved in the Regulation of Gene
Expression, Proliferation and Cell Death
Sergei N. Orlov, Olga A. Akimova and Pavel Hamet
Vascular remodeling and hypertrophy/hyperplasia of the heart
and kidney are known to be major servomechanisms of long-term
maintenance of elevated blood pressure and the development
of cardiovascular and renal complications seen in hypertension.
Several lines of evidence suggest that these abnormalities
are genetically determined and evoke an imbalance between
cell proliferation and death. During the last 2 decades, it
was shown that the level of cardiotonic steroids (CTS), i.e.
potent and selective Na+,K+-ATPase inhibitors,
is increased in several forms of volume-expanded hypertension.
We focus our review on recent data implicating CTS in the
regulation of cell proliferation and death. At low concentrations,
CTS augment proliferation of vascular smooth muscle cells
(VSMC) as well as renal epithelial and vascular endothelial
cells without significant inhibition of Na+,K+-ATPase-mediated
ion fluxes. In contrast to cell proliferation, effect of CTS
on cell survival is tissue-specific. In VSMC, CTS inhibit
programmed cell death via a novel Na+i-mediated,
Ca2+i-independent mechanism
of expression of antiapoptotic genes including mortalin, whereas
in vascular endothelial and renal epithelial cells, long-term
exposure to CTS leads to cell death showing combined markers
of apoptosis and necrosis. This mode of cell death is caused
by interaction of CTS with Na+,K+-ATPase
but is independent of inhibition of the Na+,K+-ATPase-mediated
ion fluxes and inversion of the [Na+]i/[K+]i
ratio. We propose that these novel signaling pathways triggered
by enhanced production of endogenous CTS and/or abnormal Na+
handling contribute to cardiovascular and renal complications
seen in hypertension.
[Back to top]
Diagnosis of Surgically-Treatable Forms of Primary
Aldosteronism
Paolo Mulatero, Alberto Milan, Franco Rabbia, Corrado
Garrone, Denis Rossato and Franco Veglio
Primary aldosteronism (PA) is a common form of endocrine
hypertension in which aldosterone production is inappropriate
and at least partially autonomous of the renin-angiotensin
system. Recent studies using the plasma aldosterone/plasma
renin activity (PRA) ratio (ARR) as a screening test for both
hypokalaemic and normokalaemic hypertensives have reported
a high prevalence of this disease, with PA accounting for
up to 12% of hypertensive patients. Therefore, PA is considered
the most common identifiable, specifically treatable and potentially
curable form of hypertension. Of particular interest is the
identification of the different subtypes of PA, since some
of them benefit from surgical treatment, whereas others require
medical treatment with mineralocorticoid receptor antagonists.
Herein, we review the diagnostic strategies used to identify
surgically-treatable forms of PA, i.e. those forms that display
unilateral secretion of aldosterone and benefit from unilateral
adrenalectomy. In particular, we compare the different imaging
strategies, the role of hormonal tests and the indication
and interpretation of adrenal venous sampling.
[Back to top]
SDH Genes: From Glomic Tumours to Pheochromocytomas
Alexander Persu and Miikka Vikkula
The four SDH genes encode succinate dehydrogenase
(SDHA and SDHB) and its anchoring subunits
(SDHC and SDHD), which constitute complex
II of the mitochondrial membrane, involved both in the respiratory
chain and the Krebs cycle. Mutations of SDHD and
less frequently SDHB and SDHC are at the
origin of rare hereditary forms of head and neck paraganglioma.
Interestingly, SDHB mutations are also a major cause
of sporadic and familial pheochromocytomas, which have the
same embryonic origin as head and neck paragangliomas. Patients
with SDHB mutations are at higher risk of developing
malignant and recurrent forms of pheochromocytoma.
SDHB mutations have also been found in pedigrees
harbouring both paragangliomas and renal cell carcinomas.
This association reminds us of the Von Hippel-Lindau syndrome
caused by mutations in the VHL gene. It should be
pointed out that several angiogenic factors (HIFα,
VEGF) are overexpressed both in tumours associated with paraganglioma
and Von Hippel-Lindau syndrome. Though the different steps
leading from SDH mutations to paraganglioma remain
obscure, it is tempting to hypothesise that SDH gene
products, VHL and angiogenic factors belong to the same functional
pathway.
The story of SDH genes is an impressive example
of how the unravelling of the genetic basis of a rare disease
i.e. familial head and neck paraganglioma can provide new
insights into mechanisms involved in more frequent conditions
such as endocrine hypertension, tumourigenesis, angiogenesis
and adaptation to hypoxia.
[Back to top]
A Systematic Approach to Hypertensive Urgencies and
Emergencies
Seth R. Bender, John D. Filippone, Sabine Heitz and John
D. Bisognano
Hypertension affects an estimated thirty percent of all
Americans, a number expected to climb as the population ages.
At some point in their life, approximately one percent of
these patients will experience a hypertensive crisis-either
a hypertensive urgency or emergency. These rapid and worrisome
elevations in blood pressure account for many visits to emergency
departments and urgent treatment in primary care settings.
Patients with hypertensive crises may be asymptomatic, or
may present with encephalopathy, chest pain, heart failure,
headache, epistaxis, and a number of other clinical disorders.
The approach to treating these patients varies widely throughout
the world, primarily because of the lack of quality clinical
trial data that guides the treatment of this fairly large
population of patients with hypertensive crises.
In this paper, the categorization of hypertensive urgencies
and emergencies will be reviewed. While the majority of the
patients have longstanding primary hypertension with sometimes
erratic and inadequate treatment, the hypertensive crisis
may also be an indicator of another underlying clinical process.
The pathophysiology and epidemiology of these conditions will
be discussed. The current guidelines for treatment will be
summarized. Additionally, the use and indications for various
parenteral and intravenous drugs will be described.
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