Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 2, Number 3, August 2006
Contents
Barker and Brenner: A Basis for Hypertension? Pp.
179-185
Karen M. Moritz and John F. Bertram
[Abstract]
Regressing Left Ventricular Hypertrophy: The Role of Telmisartan
and Other ARBs Pp. 187-192
Domenico Galzerano, Paolo Tammaro, Diana Lama, De Martino
Carmen, Antonio Galzerano, Roberto Breglio and Paolo Capogrosso
[Abstract]
Neurotransmission Alterations in Central Cardiovascular
Control in Experimental Hypertension Pp. 193-198
Ruy Ribeiro de Campos and Cassia T. Bergamaschi
[Abstract]
Obesity-Associated Hypertension in Childhood: A New Epidemic
Problem Pp. 199-206
Simonetta Genovesi and Federico Pieruzzi
[Abstract]
Clinical and Pre-clinical Applications of the Transcendental
Meditation Program®
in the Prevention and Treatment of Essential Hypertension
and Cardiovascular Disease in Youth and Adults Pp.
207-218
Vernon A. Barnes and David W. Orme-Johnson
[Abstract]
The Renin-Angiotensin System: Emerging Concepts Pp.
219-226
Robson A.S. Santos, Maria José Campagnole-Santos,
Sérgio V.B. Pinheiro and Anderson J. Ferreira
[Abstract]
Renal Cytochrome P450-Derived Eicosanoids and Hypertension
Pp. 227-236
Mong-Heng Wang
[Abstract]
Relationship Between Hypertension and Atherosclerosis: From
a Viewpoint of the Most Potent Vasoconstrictor Human Urotensin
II Pp. 237-246
Takuya Watanabe, Tomoko Kanome and Akira Miyazaki
[Abstract]
D3 Dopamine Receptor and Essential Hypertension
Pp. 247-253
Chunyu Zeng, Gilbert M. Eisner, Robin A. Felder and Pedro
A. Jose
[Abstract]
Abstracts
[Back to top]
Barker and Brenner: A Basis for Hypertension?
Karen M. Moritz and John F. Bertram
In the large majority of cases, the underlying cause
of hypertension is unknown. In the late 1980’s, Barry
Brenner and colleagues suggested that individuals with a reduced
nephron endowment were more likely to develop hypertension.
This was followed soon after by the report from epidemiologist,
David Barker and co-workers, of a link between low birth weight
and an increased risk of adult cardiovascular disease, including
hypertension. It was proposed that a low birth weight was
indicative of a fetus having been exposed to a suboptimal
intrauterine environment and somehow being “programmed”
to develop adult disease. What is the evidence for a link
between these two hypotheses, and does low birth weight, associated
with a decrease in nephron endowment, provide in part, a basis
for essential hypertension? In the past 20 years, intensive
clinical and basic research has attempted to answer these
questions using a variety of approaches. In normal human populations,
low birth weight has been correlated with a low nephron number
and both these factors have been shown to be associated with
elevated blood pressure in adulthood. Animal models, especially
those employing maternal protein deficiency or glucocorticoid
exposure, have in general reproduced this phenomenon with
offspring born of low birth weight having a reduced nephron
number and hypertension in adulthood. However, experimental
evidence is accumulating that low birth weight and a reduction
in nephron endowment can occur independently of one another
and do not always result in adult hypertension. In particular,
the timing and nature of the in utero insult, the
gender of the fetus and the subsequent postnatal environment
may modify the outcome significantly.
[Back to top]
Regressing Left Ventricular Hypertrophy:
The Role of Telmisartan and Other ARBs
Domenico Galzerano, Paolo Tammaro, Diana Lama, De
Martino Carmen, Antonio Galzerano, Roberto Breglio and Paolo
Capogrosso
Left ventricular hypertrophy (LVH) is a common form of
target organ damage associated with hypertension that increases
the risk for cardiovascular morbidity and mortality. Regression
of left ventricular mass (LVM) substantially reduces this
risk, and antihypertensive treatment is associated with reduction
in LVM. Identifying the optimal therapeutic strategy that
brings effective BP reductions and superior LVM regression
is therefore important for the effective management of patients
with LVH. Hypertension, both mean load and variability (for
example, the early morning blood pressure [BP] surge), causes
LVH. LVH also results from abnormalities in neurohormonal
systems (such as the renin-angiotensin-aldosterone system
[RAAS]), and metabolic abnormalities. Agents that block the
RAAS (angiotensin receptor blockers [ARBs], angiotensin-converting
enzyme inhibitors) have particular efficacy. Telmisartan is
a long-acting ARB that has shown regression of LVH and improved
diastolic function in several clinical trials. Compared with
carvedilol, telmisartan induces more regression of LVM for
the same degree of BP control, and compared with hydrochlorothiazide
the regression of LVM for a given degree of BP lowering is
greater. As part of the ONTARGET study that compares telmisartan,
ramipril, and the combination, a substudy will assess the
effects of the three therapeutic strategies on the regression
of LVH.
[Back to top]
Neurotransmission Alterations in Central Cardiovascular
Control in Experimental Hypertension
Ruy Ribeiro de Campos and Cassia T. Bergamaschi
The brain pathways involved in the control of arterial
blood pressure and sympathetic nerve activity are distributed
throughout the central nervous system and are organized in
topographically selective ensembles of premotor neurons. There
is increasing evidence to support the notion that increased
sympathetic nerve activity plays an important role in the
pathogenesis of human and experimental hypertension. In this
review, we will focus on the importance of two distinct populations
of sympathetic premotor neurons, those of the rostral ventrolateral
medulla and those of the paraventricular nucleus of the hypothalamus,
in the genesis and maintenance of experimental hypertension.
The rostral ventrolateral medulla and paraventricular nucleus
of the hypothalamus contain the principal premotor neurons
involved in the modulation of sympathetic vasomotor tone and
arterial blood pressure. Therefore, changes in the excitatory
or inhibitory neurotransmission within these two nuclei might
constitute a mechanism that is essential for the development
and maintenance of hypertension. The present review addresses
this hypothesis.
[Back to top]
Obesity-Associated Hypertension in Childhood:
A New Epidemic Problem
Simonetta Genovesi and Federico Pieruzzi
In recent years, opinions on hypertension in the paediatric
age range have been changing. Although secondary forms of
childhood hypertension maintain important clinical relevance,
lately much more attention has been paid to primary forms
of high blood pressure in children. At present, the prevalence
of primary hypertension in children is not easily defined,
also because of an unsatisfactory knowledge of this phenomenon.
A child with elevated blood pressure values shows a high probability
of developing hypertension in adulthood. Many factors that
contribute to the development and maintenance of hypertension
in the adult population are already present and operating
in childhood. Overweight is one of the most important of these
factors. In the industrialised countries, prevalence of childhood
overweight has increased markedly during the last five decades
and as in adults, overweight is related to several cardiovascular
risk factors in children too.
For these reasons, it may be important to precisely identify
the children with high blood pressure values and body weight
excess that might develop cardiovascular diseases in adulthood,
and thus allow activation of preventive measures and therapeutic
interventions that may reduce morbidity and mortality related
to cardiovascular diseases.
[Back to top]
Clinical and Pre-clinical Applications of
the Transcendental Meditation Program®
in the Prevention and Treatment of Essential Hypertension
and Cardiovascular Disease in Youth and Adults
Vernon A. Barnes and David W. Orme-Johnson
Acute and chronic environmental and psychosocial stress
contributes to the pathogenesis and progression of cardiovascular
diseases (CVD). Stress reduction via Transcendental Meditation
(TM)® has been shown to lower blood pressure (BP) levels
and reduce CVD risk in adults and adolescents. This article
reviews recent findings indicating a beneficial BP-lowering
impact of TM in hypertensive adults at rest and in pre-hypertensive
adolescents at rest, during acute laboratory stress and during
normal daily activity. These findings have important implications
for inclusion of TM in efforts to prevent and treat cardiovascular
diseases and its clinical consequences.
[Back to top]
The Renin-Angiotensin System: Emerging Concepts
Robson A.S. Santos, Maria José Campagnole-Santos,
Sérgio V.B. Pinheiro and Anderson J. Ferreira
The renin-angiotensin system (RAS) is a pivotal
regulator of the renal and cardiovascular functions playing
an important role in the control of blood pressure and hydroelectrolyte
balance. In the past few years the combination of classical
physiopharmacological techniques with modern genomics and
protein chemistry methods has lead to the identification of
important novel components of the RAS: the Angiotensin (Ang)
IV binding site IRAP (insulin-regulated aminopeptidase), the
angiotensin-converting enzyme 2 (ACE2), and the Ang-(1-7)
receptor Mas. Ang-(1-7) is one of the most interesting peptide
fragments of the RAS because it has actions which are often
opposite to those of Ang II. The recent identification of
the Ang-(1-7) forming enzyme ACE2 and of Mas as an Ang-(1-7)
receptor has added further support and more widely acceptance
to a new concept of the RAS in which the system has two major
arms: a vasoconstrictor/proliferative in which the major player
is Ang II and a vasodilator/anti-proliferative in which the
major effector is Ang-(1-7). In this article we will briefly
review these novel aspects related to the RAS with focus on
the possible physiological role of the ACE2-Ang-(1-7)-Mas
axis in the cardiovascular system.
[Back to top]
Renal Cytochrome P450-Derived Eicosanoids
and Hypertension
Mong-Heng Wang
The cytochrome P450 (CYP) monooxygenase system represents
a major metabolic pathway of arachidonic acid in the kidney.
The primary CYP monooxygenase-derived arachidonic acid metabolites
(eicosanoids) in renal tubular and vascular tissues are hydroxyeicosatetraenoic
acids (HETEs) and epoxyeicosatrienoic acids (EETs), which
are further me-tabolized by epoxide hydrolase to dihydroxyeicosatrienoic
acids (DHETs). CYP-derived eicosanoids have been shown to
affect vascular tone and tubular epithelial transport, contribute
to the regulation of renal function, and participate in the
long-term control of blood pressure. This review will focus
on the biochemistry, pharmacology, and physiological significance
of the CYP-derived eicosanoids in the mammalian kidney. In
addition, we will also discuss the role of these metabolites
in pregnancy- and obesity-induced hypertension in animal models,
and in human hypertension.
[Back to top]
Relationship Between Hypertension and Atherosclerosis:
From a Viewpoint of the Most Potent Vasoconstrictor Human
Urotensin II
Takuya Watanabe, Tomoko Kanome and Akira Miyazaki
Human urotensin II (U-II), the most potent vasoconstrictor
peptide identified to date, and its receptor (UT) are involved
in etiology of hypertension. In hypertensive patients, U-II
induces vasoconstriction in forearm brachial artery infusion
studies. Recent studies demonstrated elevated plasma U-II
concentrations in patients with hypertension, diabetes mellitus,
atherosclerosis, and coronary artery disease. U-II is expressed
in endothelial cells, macrophages, macrophage-derived foam
cells, and myointimal and medial vascular smooth muscle cells
(VSMCs) of atherosclerotic human coronary arteries. UT receptors
are present in VSMCs of human coronary arteries, thoracic
aorta and cardiac myocytes. Lymphocytes are the most active
producers of U-II, whereas monocytes and macrophages are the
major cell types expressing UT receptors, with relatively
little receptor expression in foam cells, lymphocytes, and
platelets. U-II accelerates foam cell formation by up-regulation
of acyl-coenzyme A:cholesterol acyltransferase-1 in human
monocyte-derived macrophages, and stimulates cell growth and
up-regulates type 1 collagen expression in human endothelial
cells. U-II also activates NADPH oxidase and plasminogen activator
inhibitor-1 in human VSMCs, and stimulates VSMC proliferation
with synergistic effects observed when combined with oxidized
LDL, reactive oxygen species and serotonin. These findings
suggest that U-II plays key roles in accelerating the development
of atherosclerosis, and hence coronary artery disease.
[Back to top]
D3 Dopamine Receptor and Essential Hypertension
Chunyu Zeng, Gilbert M. Eisner, Robin A. Felder and
Pedro A. Jose
Dopamine receptors are expressed in a number of
organs and tissues; the peripheral dopamine receptors influence
cardiovascular and renal function by decreasing preload and
afterload and by regulating fluid and electrolyte transport.
Most of the knowledge on these actions of dopamine has been
garnered from studies of D1-like dopamine receptors.
The D3 dopamine receptor subtype, which belongs
to the D2-like receptor subfamily, has been extensively
studied in the neuro-sciences. Recently, the peripheral actions
of the D3 receptor have also raised considerable
interest. Previous studies showed that the D3 receptor
is expressed in organs outside the central nervous system
such as the kidneys and blood vessels. Activation of the D3
receptor, alone or in synergism with D1 receptor
induces diuresis and natriuresis and dilates resistance vessels.
The D3 receptor also interacts positively with
endothelin type B receptors and negatively with the renin-angiotensin-aldosterone
system. For example, the D3 receptor-mediated natriuresis
can be blocked by ETB receptor antagonists and stimulation
of the D3 receptor decreases AT1 receptor
expression in renal proximal tubule cells and inhibits renin
and aldosterone secretion. The high blood pressure observed
in spontaneously hypertensive rats and D3 receptor
deficient mice, may, in part, be caused by impaired D3
receptor-mediated renal sodium excretion, impaired interaction
with D1 and ETB receptors and impaired inhibition
of the renin-angiotensin-aldosterone system. In this review,
we examine the role of the peripheral D3 receptor
in the regulation of renal sodium excretion and vascular resistance,
and its interaction with the renin-angiotensin system and
other dopamine receptor subtypes. We also present our current
understanding of the role of D3 receptor in the
pathophysiology of human essential hypertension.
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