Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension
Reviews
Volume 1, Number 1, 2005
Contents
Glucocorticoid-Induced Hypertension and Tetrahydrobiopterin
(BH4), a Common Cofactor for the Production of Vasoactive
Molecules Pp. 1-6
Brett M. Mitchell and Clinton Webb
[Abstract] [Full
text article]
Natriuretic Peptides in Heart Failure and Post-Myocardial
Infarction Pp. 7-13
Paul Lijnen, Guillermo Diaz-Arayax, Victor Petrov and
Robert Fagard
[Abstract] [Full
text article]
Role of NADPH Oxidase in Hypertension and Diabetic
Nephropathy Pp. 15-20
Maristela L. Onozato and Akihiro Tojo
[Abstract] [Full
text article]
Discovering the Genetics of Complex Disorders Through
Integration of Genomic Mapping and Transcriptional Profiling
Pp. 21-34
Robert S. Danziger, Ming You and Huda Akil
[Abstract] [Full
text article]
Functional Genomics of Blood Pressure Determination:
Dissecting and Assembling a Polygenic Trait by Experimental
Genetics Pp. 35-50
Alan Y. Deng
[Abstract] [Full
text article]
Extracellular Matrix Remodeling in Hypertension Pp.
51-60
Hiroyuki Sasamura, Ryoko Shimizu-Hirota and Takao Saruta
[Abstract] [Full
text article]
Effect of the Antihypertensive Treatment on the Bone
Mineral Density and Osteoporotic Fracture Pp. 61-66
Jose L. Perez-Castrillon and Isabel Justo, Alberto Sanz-Cantalapiedra,
Carol Pueyo, Gonzalo Hernandez and Antonio Duenas
[Abstract] [Full
text article]
Renoprotection with Anti-Hypertensives: Reduction
of Proteinuria and Improvement of Oxygenation via Inhibition
of the Renin-Angiotensin System Pp. 67-76
Masaomi Nangaku, Takamoto Ohse, Tetsuhiro Tanaka, Ichiro
Kojima and Toshiro Fujita
[Abstract] [Full
text article]
Issues and Progress in Isolation of Susceptibility
Genes of Essential Hypertension Pp. 77-87
Tomohiro Nakayama
[Abstract] [Full
text article]
How Should Serum Uric Acid Concentrations be Interpreted
in Patients with Hypertension? Pp. 89-95
William S. Waring and
Shahana Esmail
[Abstract] [Full
text article]
Abstracts
[Back to top]
Glucocorticoid-Induced Hypertension and Tetrahydrobiopterin
(BH4), a Common Cofactor for the Production of Vasoactive
Molecules
Brett M. Mitchell and Clinton Webb
[Full
text article]
Excess glucocorticoids, whether produced endogenously or
over-prescribed for immunosupression and antiinflammation,
can lead to hypertension and cardiovascular disease. Humans
and animals with glucocorticoid-induced hypertension exhibit
reduced nitric oxide (NO) and serotonin, and have increased
sensitivity to catecholamines. Thecommon cofactor for the
production of these vasoactive molecules is tetrahydrobiopterin
(BH4). Recent research has focused on the effects of excess
glucocorticoids on BH4 biosynthesis because reduced BH4 cofactor
levels can alter the production of NO, serotonin, and catecholamines
by NO synthase and the aromatic amino acid hydroxylases. This
review will focus on the mechanisms and consequences of excess
glucocorticoids on the BH4 biosynthesis pathway and the enzymes
that utilize BH4 as a cofactor. Alterations in the production
of BH4 contribute to glucocorticoid-induced hypertension and
an understanding of the mechanisms may provide therapeutic
targets to either develop synthetic glucocorticoids that do
not affect BH4 biosynthesis or increase BH4 levels in conditions
where glucocorticoids are elevated.
[Back to top]
Natriuretic Peptides in Heart Failure and Post-Myocardial
Infarction
Paul Lijnen, Guillermo Diaz-Arayax, Victor Petrov and
Robert Fagard
[Full
text article]
The heart is a major site of natriuretic peptides (NP).
Atrial and brain natriuretic peptide (ANP and BNP) are predominantly
produced by atria and ventricles. C-Natriuretic peptide (CNP)
is also found in heart tissue. ANP and BNP are produced by
cardiomyocytes and fibroblasts. Cardiac fibroblasts also secrete
CNP. Three NP-receptors (NPR-A, NPRB, NPR-C) are expressed
in heart atria and ventricles.
[Back to top]
Role of NADPH Oxidase in Hypertension
and Diabetic Nephropathy
Maristela L. Onozato and Akihiro Tojo
[Full
text article]
Oxidative stress plays an important role in the development
of renal damage in diabetes and hypertension. The major source
of oxidative stress is nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase-derived superoxide anion (O2 .-) that directly
damage cell and also activate signaling of cell proliferation,
adhesion molecules, and fibrosis. O2 .- also inactivates endothelium
derived nitric oxide and cause endothelial nitric oxide synthase
uncoupling. In the spontaneously hypertensive rat and Dahl
salt-sensitive hypertensive rat with heart failure and in
the streptozotocininduced diabetic rats NADPH oxidase is increased
via increased renal angiotensin II (AngII), and angiotensin
converting enzyme inhibitor (ACEI) or AngII AT1 receptor blocker
(ARB) confer renal protection by decrease in NADPH oxidase
expression. Hypercholesterolemia additively increases NADPH
oxidase in diabetes, as well as increases the adhesion molecule
ICAM-1 and glomerular macrophage infiltration. Antioxidant
drugs including apocynin, an inhibitor of the translocation
of cytosolic components of NADPH oxidase, p38 MAPK inhibitor,
or tempol, a superoxide dismutase mimetic, also show renoprotective
effect in diabetes or in hypertension. In summary, stimulation
of NADPH oxidase by renal AngII has a common pathogenic role
in the development of renal damage in hypertension and diabetes
and suppression of renal NADPH oxidase is a promising strategy
against renal damage.
[Back to top]
Discovering the Genetics of Complex Disorders Through
Integration of Genomic Mapping and Transcriptional Profiling
Robert S. Danziger, Ming You and Huda Akil
[Full
text article]
Discovering the genes that contribute to complex polygenic
diseases represents a significant challenge. Investigating
the structural genetic variations associated with these disorders
may not be sufficiently informative about vulnerability genes
modulated by the environment. Characterizing gene expression
patterns does not identify the primary differences in gene
structure. The convergence of global screening of gene expression
patterns with extensive structural genomic information may
be necessary to identify the gene clusters that contribute
to these pervasive diseases. These integrative efforts, though
promising, are in their early phases and will require further
refinement.
[Back to top]
Functional Genomics of Blood Pressure
Determination: Dissecting and Assembling a Polygenic Trait
by Experimental Genetics
Alan Y. Deng
[Full
text article]
Major accomplishments in sequencing mammalian genomes have
ushered in the era of post-genomics. With it, the mechanics
of positional cloning could soon be transformed into simply
querying databases, an emerging strategy of gene identifications
from a sequence to implicating a gene function. An encyclopedic
collection of sequences and everevolving innovations in genome
technologies have raised expectations for experimental models
to reveal mechanisms underlying polygenic hypertension. In
synchrony with the build-up of genomic infrastructures and
analytical tools, the development of genetic models has also
become refined, sophisticated and even more indispensable,
as they provide substrates in vivo for functional genomics.
In addition to gene discovery, the mechanisms establishing
relationships among quantitative trait loci (QTLs) for blood
pressure (BP) can be established and validated in the context
of an integrated physiological system. Genetic analyses by
congenic strains have illustrated a highly complex and hierarchical
organization among BP QTLs. These genes do no function in
isolation, but act in concert via epistatic and additive interactions
with one another. The understanding of complex QTL interactions
will facilitate rationally targeted pharmacological designs
and clinical treatment of hypertension. Identifications of
these QTLs will provide new therapeutic targets and genetically
oriented diagnostic tools.
[Back to top]
Extracellular Matrix Remodeling in Hypertension
Hiroyuki Sasamura, Ryoko Shimizu-Hirota and Takao Saruta
[Full
text article]
Increases in arterial blood pressure cause cumulative changes
in tissue structure and function, resulting ultimately in
end-organ damage. One of the pathological hallmarks of hypertensive
tissue injury is an increase in tissue fibrosis, which leads
to reductions in tissue compliance and function. Fibrosis
(or sclerosis) occurs as result of marked changes in the amount
and composition of the extracellular matrix. This extracellular
matrix is a complex mixture of structural proteins and glycoproteins,
including collagens, fibronectins, and proteoglycans. Hypertension
is known to be associated with increases in the synthesis
of extracellular matrix proteins and changes in their degradation.
These processes are mediated by several mediators, in particular
the renin-angiotensin-aldosterone system. Since these changes
play an important role in the formation of vascular sclerosis,
cardiac dysfunction, and renal damage, understanding the mechanisms,
and finding interventions to prevent or reverse these changes
are clinically important. In this review we discuss the alterations
in the extracellular matrix during hypertension, as well as
the effects of antihypertensive agents in animal models and
human patients.
[Back to top]
Effect of the Antihypertensive Treatment on the Bone
Mineral Density and Osteoporotic Fracture
Jose L. Perez-Castrillon and Isabel Justo, Alberto Sanz-Cantalapiedra,
Carol Pueyo, Gonzalo Hernandez and Antonio Duenas
[Full
text article]
The financial and social cost of hypertension and osteoporosis,
clinically silent diseases, are determined by the consequences,
such as a vascular disease and fractures. The relationship
between these illnesses has not been clearly established,
although many alterations in extracellular metabolism of calcium,
which could determine the level of bone mineral density (BMD)
in these patients, have been associated to hypertension. Despite
these alterations, the lack of studies relating these two
important diseases is surprising, and hypertension is not
identified as a risk factor for osteoporosis.
Interestingly, there is a lack of information of the long-term
effects of antihypertensive treatment on bone mineral density,
although 50 % of the hypertensive population is made up of
postmenopausal women. Most studies analyzed the effects of
thiazides and, to a lesser degree, the effects of calcium
antagonist.
The purpose of this review
is evaluate the effect of the antihypertensive therapeutic
group (diuretics, b-blockers, calcium antagonists, angiotensin
converting enzyme) on the bone mineral density (BMD) and osteoporotic
fracture.
[Back to top]
Renoprotection with Anti-Hypertensives: Reduction
of Proteinuria and Improvement of Oxygenation via Inhibition
of the Renin-Angiotensin System
Masaomi Nangaku, Takamoto Ohse, Tetsuhiro Tanaka, Ichiro
Kojima and Toshiro Fujita
[Full text article]
Hypertension is a common cause of chronic kidney disease
(CKD) and even more common sequelae of CKD. While strict control
of blood pressure is essential to preserve residual renal
function, numerous clinical trials have demonstrated that
inhibitors of the renin-angiotensin system (RAS), i.e. angiontensin
converting enzyme inhibitors (ACEi) and angiotensin receptor
blockers (ARB), reduce the progression of CKD. These studies
have examined type I and type II diabetic as well as non-diabetic
nephropathies, utilizing end points such as serum creatinine,
glomerular filtration rate, time to end-stage renal disease
(ESRD), and death. These observations suggest that drugs blocking
the RAS offer advantages beyond lowering blood pressure in
diabetic and non-diabetic CKD. Therefore, guidelines recommend
antihypertensives that block RAS in patients with CKD.
Previous studies emphasized amelioration of glomerulosclerosis
induced by glomerular hypertension as a renoprotective mechanism
of inhibition of RAS. It should also be noted that progression
to ESRD is mediated by two final common pathways; tubulointerstitial
injury induced by proteinuria, and chronic hypoxia in the
tubulointerstitium. Recent research indicates that reduction
of proteinuria and improvement of oxygenation of the kidney
are crucial mechanisms by which inhibition of RAS mediates
renoprotection providing additional rationale for the use
of ACEi and ARB to protect the kidney.
[Back to top]
Issues and Progress in Isolation of Susceptibility
Genes of Essential Hypertension
Tomohiro Nakayama
[Full
text article]
Essential hypertension (EH) is thought to be a multifactorial
disease. In Japan, there are more than 20 million cases of
EH, which accounts for 80 to 90% of hypertension cases in
Japan. It is very difficult to isolate the susceptibility
genes of EH in familial linkage analysis such as sib-pair
analysis and association studies such as case-control studies
of candidate genes. Whole genome scanning and haplotype analysis
using genetic markers will be widely conducted in the future.
The present paper contains a review of issues and progress
in isolation of susceptibility genes of EH, and an introduction
to an effective novel method for isolation of susceptibility
genes of EH.
[Back to top]
How Should Serum Uric Acid Concentrations be Interpreted
in Patients with Hypertension?
William S. Waring and Shahana Esmail
[Full
text article]
A large number of epidemiological
studies have identified an association between high serum
uric acid (SUA) concentrations and increased cardiovascular
risk. However, the significance of this relationship has been
difficult to interpret due to the co-existence of other cardiovascular
risk factors. The relationship between SUA concentrations
and morbidity appears particularly strong in patients with
hypertension, and a number of recent studies have found that
this relationship persists after adjusting for potential confounders.
This paper reviews the potential mechanisms by which SUA might
be causally related to cardiovascular disease in patients
with hypertension. We critically appraise the evidence in
favour of a causal, coincidental or compensatory relationship,
and consider the potential outcomes of lowering SUA in patients
with hypertension. The potential consequences of high SUA
concentrations are discussed and, based on existing evidence,
consideration is given to the potential therapeutic value
of strategies to lower SUA as a means of cardiovascular risk
reduction in patients with hypertension.
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