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Current Hypertension
Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 6, Number 4, November 2010
Contents
New Advances in Blockade of the Renin-Angiotensin System –
the Role of Direct Renin Inhibition Pp. 222-231
Louise F. Clark, Gordon F. Rushworth, Stephen J. Leslie
and Sandra MacRury
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Article]
Hypertension: Basics Concepts and the Evolving
Role of Novel Treatments Pp. 232-237
Marie-Françoise Doursout, Emil Martin, Iraida Sharina,
Ka Bian and Ferid Murad
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Article]
A Proposal----The Renal Kallikrein-Kinin System
as a Compensating System for Salt Accumulation after Excess
Salt Intake Pp. 238-250
Makoto Katori and Masataka Majima
[Abstract] [Purchase
Article]
Clinical Significance of the Cardio-Ankle Vascular
Index (CAVI) in Hypertension Pp. 251-253
Kazuhiko Kotani, Michiaki Miyamoto and Nobuyuki
Taniguchi
[Abstract] [Purchase
Article]
Cardiovascular Disease in Masked Hypertension:
Clinical Implications Pp. 254-259
Cheol Ung Choi and Chang Gyu Park
[Abstract] [Purchase
Article]
The Na+/Ca2+ Exchanger Mediates the Effects of
Oxidative Stress in Hypertension Pp. 260-265
Remo George, Todd Casanova, Kathy Nugent and
M. Tino Unlap
[Abstract] [Purchase
Article]
Central Arterial Aging and Angiotensin II Signaling
Pp. 266-281
Mingyi Wang, Benjamin Khazan and Edward G. Lakatta
[Abstract] [Purchase
Article]
Role of Epigenetic Regulatory Mechanisms in the
Mechanism of Essential Hypertension Pp. 282-284
Zhong Guang-Wei, Luo Yan-Hong, Li Wei, Zhong Chang-Gao
and Zhang Cheng
[Abstract] [Full
Text Article]
Abstracts
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New Advances in Blockade of the Renin-Angiotensin
System – the Role of Direct Renin Inhibition
Louise F. Clark, Gordon F. Rushworth, Stephen J. Leslie
and Sandra MacRury
Direct Renin Inhibitors (DRIs) are a new class of medication,
and are the first which block the rate-limiting step of the
renin-angiotensin-aldosterone-system (RAAS). Aliskiren, the
first licensed orally active DRI, has been shown to be an
effective antihypertensive agent. This review article outlines
the pharmacological basis for DRI therapy, from discovery
of the class to ongoing clinical trials and novel therapeutic
applications of aliskiren.
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Hypertension: Basics Concepts and the Evolving
Role of Novel Treatments
Marie-Françoise Doursout, Emil Martin, Iraida Sharina,
Ka Bian and Ferid Murad
Hypertension, a major cardiovascular risk factor, is the primarily
cause of mortality worldwide. A large body of evidence indicates
that patients with essential hypertension, and even more those
with complicated hypertension, are characterized by endothelial
dysfunction due to impaired nitric oxide (NO) availability
secondary to oxidative stress production. Therefore, a dysfunctioning
endothelium is an early marker in the development of cardiovascular
events. This observation suggest that treatment strategies
that improve endothelial function would exert beneficial effects
in hypertensive subjects, and may also help to prevent the
development of hypertension and its cardiovascular complications.
Part I of the present review describes the etiology of hypertension
as well as the role of NO in the physio-pathology of the endothelium
whereas in Part II, we are reporting novel treatments e.g.
beta-blockers, ACE inhibitors, calcium channel an-tagonists,
NO therapies, selective inhibitors of PDE Type 5, statins
and regular aerobic physical exercise to the event to improve
or restore endothelial function. In the near future, large
scale clinical trials are required to demonstrate that treatment
of endothelial dysfunction can lead to better prognosis in
patients with essential hypertension.
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A Proposal----The Renal Kallikrein-Kinin System
as a Compensating System for Salt Accumulation after Excess
Salt Intake
Makoto Katori and Masataka Majima
Terrestrial mammals, like human, must reserve water and NaCl
to counter the effects of dry-environments. Their kidneys
need to reabsorb as much water and sodium as possible along
the proximal tubules and collecting duct. Thus, excess sodium
intake tends to sodium accumulation in the body. The renal
(tissue) kallikrein-kinin system (KKS) exists to prevent excessive
sodium reabsorption. Renal kallikrein is secreted from the
distal connecting tubule cells, which are located just distal
to the major reabsorbing system. Kallikrein releases kinins,
which inhibit sodium reabsorption along the collecting ducts.
The kinins in the tubules are quickly destroyed by kidney-specific
destroying enzymes (kininases), carboxypeptidase Y-like exopeptidase
and neutral endopeptidase, which differ completely from those
in plasma. Ebelactone B and poststatin were discovered as
selective inhibitors of urinary kininases. Excess sodium intake
causes hypertension, since sodium accumulation in the blood
vessel walls increases sensitivity to hypertensive agents.
Potassium, and ATP-sensitive potassium channel blockers cause
renal kallikrein secretion. In bradykinin B2 receptor gene
knockout mice, tissue kallikrein gene knockout mice, and kininogen-deficient
rats, the knockout or deficiency does not itself induce hypertension,
but these animals are salt-sensitive. Mutant kininogen-deficient
(kinin-free) rats on 2% sodium intake quickly develop hypertension.
Urinary kininase inhibitors reduce high blood pressure due
to sodium accumulation on high sodium intake. Our ample supporting
data suggest that the renal KKS prevents sodium accumulation,
and that reduced levels of renal kallikrein may cause salt-sensitive
hypertension.
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Clinical Significance of the Cardio-Ankle Vascular
Index (CAVI) in Hypertension
Kazuhiko Kotani, Michiaki Miyamoto and Nobuyuki
Taniguchi
Increased blood pressure and hypertension are a major atherosclerotic
risk factor. Arterial stiffness is recognized to be reflective
to the atherosclerotic states. The pulse wave velocity (PWV)
is a noninvasive, simple, easy and reproducible index that
can be used to assess arterial stiffness in association with
blood pressure. The cardio-ankle vascular index (CAVI) has
recently been developed to evaluate arterial stiffness similarly
to PWV, but theoretically, this index is less influenced by
blood pressure. There have been several clinical reports on
the use of the CAVI in patients with hypertension. The CAVI
levels are reported to be significantly and positively correlated
with the ultrasonographical atherosclerotic parameters of
carotid arteries, as a surrogate marker of atherosclerotic
events, in hypertensive patients. Intervention studies of
anti-hypertensive therapy using CAVI have shown that candesartan,
olmesartan and efonidipine can improve the CAVI levels. These
results suggest that the CAVI is clinically helpful for the
assessment of atherosclerotic risk and the management with
drug treatment in patients with hypertension. However, compared
with PWV, there is not much evidence of using CAVI in a clinical
setting; future research is therefore necessary.
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Cardiovascular Disease in Masked Hypertension:
Clinical Implications
Cheol Ung Choi and Chang Gyu Park
In this review, we describe target organ damage and cardiovascular
events in masked hypertension. Masked hypertension is associated
with more target organ damage, including sustained hypertension,
left ventricular hypertrophy, carotid atherosclerosis, microalbuminuria,
silent cerebral infarct, arterial stiffness, central blood
pressure and obstructive sleep apnea, than is sustained normotension.
Masked hypertension represents a strong predictor of cardiovascular
morbidity and mortality in diverse patient groups including
diabetics and patients with prehypertension. Therefore, clinicians
should pursue the diagnosis of masked hypertension in individuals
at increased cardiovascular risk and follow patients with
prehypertension, encouraging out-of-office monitoring of blood
pressure.
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The Na+/Ca2+ Exchanger Mediates the Effects of
Oxidative Stress in Hypertension
Remo George, Todd Casanova, Kathy Nugent and
M. Tino Unlap
Oxidative stress is characterized by the elevation of reactive
oxygen species (ROS) including the superoxide anion, hydrogen
peroxide and the hydroxyl radical. In almost all animal models
of hypertension and humans, reducing oxidative stress with
antioxidants will lower blood pressure and elevating oxidative
stress increases the blood pressure. Generation of ROS in
the renal vasculature is accomplished through NADPH oxidase
which is expressed in macula densa and afferent arterioles
(AA) and leads to enhanced arteriolar tone and reactivity
which precede the onset of hypertension. The underlying mechanism
is proposed to involve enhanced tubuloglomeruar feedback (TGF)
through depletion of NO through interaction with superoxide
anion in the juxtaglomerular apparatus (JGA) to form peroxynitrite
and a number of microvascular mechanisms including abnormal
elevation of intracellular calcium concentration ([Ca2+]i)
which can lead to an increased vascular tone and remodeling.
The Na+/Ca2+ exchanger (NCX) is critical in regulating cytosolic
calcium homeostasis and our studies show that oxidative stress-induced
dysregulation of cytosolic calcium homeostasis is mediated
through increased Ca2+ influx through the NCX, an effect which
is more pronounced in cells expressing an NCX isoform that
is expressed in Salt Sensitive Dahl rat. Ca2+ influx through
the NCX is preceded by elevation of intracellular Na+ (Nai)
and membrane depolarization. Because of the proximity of the
Na+/K+-ATPase and the NCX in the PLasmERo-some, it is likely
that oxidative stress-induced [Ca2+]i elevation in AA smooth
muscle cells is initiated by oxidative stress-induced inhibition
of the Na+/K+-ATPase which increases Nai that leads to membrane
depolarization and Ca2+ influx through the NCX.
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Central Arterial Aging and Angiotensin II Signaling
Mingyi Wang, Benjamin Khazan and Edward G. Lakatta
Arterial remodeling over time is a cornerstone of normal systemic
aging. The age-associated arterial structural and functional
changes in the intima, the media, and the adventitia are closely
linked to angiotensin II (Ang II) signaling. A growing line
of evidence indicates that essential elements of Ang II signaling,
which encompasses milk fat globule epidermal growth factor-8,
calpain-1, transforming growth factor-β1,
matrix metalloproteinase-2/9, monocyte chemoattractant protein-1,
nicotinamide adenine dinucleotide phosphate-oxidase, and reactive
oxygen species, are upregulated within the central arterial
wall in rats, nonhuman primates, and humans during aging.
In vitro studies show that the elevation of Ang II
signaling induces the accumulation of collagen and advanced
glycated end-products, the degradation of elastin, and the
increased cell cycle disorder, invasion, and hypertrophy of
endothelial and vascular smooth muscle cells. Further, in
vivo studies demonstrate that increased Ang II signaling
accelerates arterial aging. Conversely, attenuating Ang II
signaling via an inhibition of angiotensin conversing
enzyme or a blockade of AT1 activation retards age-associated
arterial remodeling. This review attempts to integrate complex
facts of Ang II signaling within the aged central arterial
wall and may shed light on new therapeutic targets for arterial
aging.
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[Full
Text Article]
Role of Epigenetic Regulatory Mechanisms in the Mechanism
of Essential Hypertension
Zhong Guang-Wei, Luo Yan-Hong, Li Wei, Zhong Chang-Gao
and Zhang Cheng
Hypertension is among the common and leading causes of morbidity
and mortality throughout the globe. The biological process
of hypertension involves multiple physiological pathways,
each of which may be affected by multiple gene products. But
the mechanisms under this difference are still not full understood.
In recent years, some evidence has been found supporting the
involvement of epigenetic mechanisms in many cardiovascular
diseases and others. We hypothesised that epigenetic mechanisms
have been also involved in essential hypertension possibly
by suppression of and changing the relational genes with essential
hypertension.
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