Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 3, Number 1, February 2007
Contents
The Role of Myocardial Collagen Network in Hypertensive
Heart Disease Pp. 1-7
Javier Díez, Begoña López, Arantxa
González and Ramón Querejeta
[Abstract] [Full
text article]
Are Calcium Channel Blockers First-Line Drugs for
the Treatment of Hypertension and Cardiovascular Disease?
Pp. 9-13
Alejandro de la Sierra and Luis Miguel Ruilope
[Abstract] [Full
text article]
Beta-Blockers for the Treatment of Essential Hypertension:
What are the Arguments Against Their Use as First Line Therapy?
Pp. 15-20
Michel Burnier, Roberto Bullani and Bruno Vogt
[Abstract] [Full
text article]
Beta-Blockers as First Line Treatment of Hypertension:
A Proponent’s View Pp. 21-28
Steven G. Chrysant
[Abstract] [Full
text article]
Insights into the Relationship Between Hypertension
and Albuminuria Pp. 29-37
Lucinda M. Hilliard, Leileata M. Russo and Wayne D. Comper
[Abstract] [Full
text article]
Renin Inhibition as a New Strategy to Combat Cardiovascular
Disease Pp. 39-43
Shetal H. Padia and Helmy M. Siragy
[Abstract] [Full
text article]
The Epithelial Na+ Channel as a Determinant
of Blood Pressure Pp. 45-49
Timothy J. Burton, Kevin M. O’Shaughnessy and Morris
J. Brown
[Abstract] [Full
text article]
Concerning Arterial Hypertension, Homocysteine and
Paraoxonase-1 Pp. 51-57
F. Rodríguez-Esparragón, A. Caballero-Hidalgo,
Y. Hernández Trujillo, A. Macías-Reyes and J.C.
Rodríguez-Pérez
[Abstract] [Full
text article]
Hypertension in Children After Renal Transplantation
Pp. 59-68
Tomáš Seeman
[Abstract] [Full
text article]
Pathophysiology of Hypertension During Preeclampsia:
Role of Inflammatory Cytokines Pp. 69-74
Babbette D. LaMarca, Michael J. Ryan and Joey P. Granger
[Abstract] [Full
text article]
Heme Oxygenase-1: A Potential Antihypertensive Target?
Pp. 75-82
Trinity Vera and David E. Stec
[Abstract] [Full
text article]
Abstracts
[Back to top]
The Role of Myocardial Collagen Network in Hypertensive Heart
Disease
Javier Díez, Begoña López, Arantxa
González and Ramón Querejeta
[Full
text article]
It is time to recognize that the quality, not quantity, of
myocardium in hypertensive heart disease is responsible for
adverse cardiovascular events. Experimental and clinical available
data indicate that myocardial fibrosis due to the exaggerated
accumulation of collagen type I and type III fibers predisposes
to an enhanced risk of diastolic and/or systolic ventricular
dysfunction, symptomatic heart failure, ischemic heart disease,
and arrhythmias in patients with hypertensive heart disease.
Thus, management of these patients must not only focus on
detection and regression of left ventricular hypertrophy.
Far more sensible are interventions aimed to detect and target
hypertensive myocardial fibrosis. The available data on the
use of biochemical and/or imaging methodologies to address
excessive accumulation of collagen fibers in the myocardium
of hypertensive patients are promising. On the other hand,
preliminary data suggest that the goal of reducing myocardial
fibrosis is achievable in patients with hypertensive heart
disease treated with specific antihypertensive agents. Collectively,
these findings set the stage for larger trials where-in noninvasive
measures and reparative strategies of myocardial fibrosis
to prevent heart failure could prove useful.
[Back to top]
Are Calcium Channel Blockers First-Line Drugs for
the Treatment of Hypertension and Cardiovascular Disease?
Alejandro de la Sierra and Luis Miguel Ruilope
[Full
text article]
Calcium channel blockers (CCB) represent a class of drugs
widely used for treatment of hypertension and coronary heart
disease. Some case-control studies published 10 years ago
that included patients treated with short acting dihydropyridines
reported several apparently harmful actions of this class
of drugs, such as increased risk of myocardial infarction,
cancer and gastrointestinal bleeding. However, in the last
six years a large body of evidence derived from various controlled
clinical trials has clearly demonstrated that long-acting
CCB are beneficial drugs for treating hypertension and coronary
heart disease. Studies such as INSIGHT, NORDIL, ALLHAT, VALUE
and ASCOT have shown that CCB are not inferior to other antihypertensive
drug classes in preventing cardiovascular disease in hypertensives.
In fact, the combination of a CCB and an ACE inhibitor is
clearly superior in comparison to classic combination of a
diuretic and a beta-blocker. Moreover, CCB have a particularly
good profile in preventing stroke and carotid and coronary
atherosclerosis progression. Finally, the results of another
group of trials, such as INVEST, ACTION and CAMELOT have shown
that CCB decrease the risk of new events and procedures and
also impairs atherosclerosis progression when used in patients
with stable coronary heart disease.
[Back to top]
Beta-Blockers for the Treatment of Essential Hypertension:
What are the Arguments Against Their Use as First Line Therapy?
Michel Burnier, Roberto Bullani and Bruno Vogt
[Full
text article]
Beta-blockers are recommended as first line therapy in the
treatment of essential hypertension since several decades
and this recommendation has been endorsed by most if not all
national and international guideline committees. Some concerns
about their efficacy in elderly hypertensive patients have
been raised in the mid-90ies. With the recent publication
of the LIFE and ASCOT-BPLA trials showing the superiority
of a losartan-based and an amlodipine-based regimen versus
an atenolol-based regimen in preventing stroke, additional
questions have been raised about the position of beta-blockers
in the management of hypertensive patients. Conventional beta-blockers
such as atenolol have a well known negative impact on metabolic
parameters which may limit their efficacy in protecting patients
from the development of cardiovascular events. More recent
data have also suggested that atenolol leads to lesser decrease
in central blood pressures than amlodipine and this may explain
why atenolol does not provide as much protection against stroke
than calcium antagonists and angiotensin receptor blockers.
With these new evidence, it appears legitimate to call in
question the place of beta-blockers as first choice therapy
in essential hypertension.
[Back to top]
Beta-Blockers as First Line Treatment of Hypertension:
A Proponent’s View
Steven G. Chrysant
[Full
text article]
Beta-adrenergic receptor blockers are one of the oldest class
of cardiovascular drugs still in use. Several short and long-term
clinical outcomes prospective studies have demonstrated their
effectiveness and safety for the treatment of hypertension,
coronary artery disease, myocardial infarction, heart failure
and sudden death. Despite their proven benefits, some investigators
have cautioned against their use, and others, more recently,
have suggested the complete withdrawal from their use in the
treatment of hypertension. In this review, evidence based
information will be presented which will demonstrate that
beta-blockers are an effective and safe antihypertensive class
of drugs across all age, gender and race groups. In addition,
evidence will be provided that these agents are useful drugs
in the treatment of hypertensive patients with co-morbid conditions
such as diabetes mellitus, peripheral arterial disease and
lung disease, and therefore they should continue to be used
in the treatment of these patients, either alone or in combination
with other antihypertensive drugs.
[Back to top]
Insights into the Relationship Between Hypertension
and Albuminuria
Lucinda M. Hilliard, Leileata M. Russo and Wayne D. Comper
[Full
text article]
Albuminuria is the increased excretion of the serum protein
albumin into the urine. Albuminuria is classically seen as
an important diagnostic marker of declining kidney function,
however, more recently albuminuria has also been implicated
as a marker for cardiovascular and peripheral vascular disease
indicating an important link between processes governing both
cardiovascular and renal function. This review will discuss
i) a common mechanism for albuminuria that accounts for albuminuria
seen in hypertension and other albuminuric states and ii)
possible linking factors between albuminuria, hypertension
and cardiovascular disease.
[Back to top]
Renin Inhibition as a New Strategy to Combat Cardiovascular
Disease
Shetal H. Padia and Helmy M. Siragy
[Full
text article]
The renin-angiotensin system (RAS) is a major physiological
regulator of body fluid volume, electrolyte balance, and arterial
blood pressure. Systemic suppression of the RAS through angiotensin
converting-enzyme (ACE) inhibition and/or angiotensin receptor
blockade (ARB) is an established and effective therapeutic
approach for a range of cardiovascular disorders. One of the
functions of renin is to catalyze the cleavage of angiotensinogen
to angiotensin I (Ang I), which is the first and rate-limiting
step of the RAS. Ang I is then converted by ACE to angiotensin
II (Ang II), a potent endogenous vasoconstrictor. Interruption
of the formation of Ang II by renin inhibitors offers a therapeutic
profile that is distinct from that of the more well-known
RAS antagonists, since both ACE inhibition (via ACE-independent
pathways) and ARB, result in an increase in Ang II formation.
This review will focus on the development and relevant clinical
studies involving the renin inhibitors. The therapeutic implications
of renin inhibitors, either employed alone, or in combination
with ACE inhibitors or ARBs, will also be discussed.
[Back to top]
The Epithelial Na+ Channel as a Determinant
of Blood Pressure
Timothy J. Burton, Kevin M. O’Shaughnessy and Morris
J. Brown
[Full
text article]
The epithelial Na+ channel (ENaC) forms the rate
limiting step in transepithelial Na+ absorption
across aldosterone-responsive tissues such as the distal nephron.
After more than a decade of investigation it is clear that
the mechanisms of ENaC regulation are complex with an array
of ENaC-regulatory proteins having been identified. A variety
of monogenic syndromes of low renin hypertension have been
identified that serve, through different mechanisms, to up-regulate
distal tubular ENaC activity. One of the most extensively
studied, Liddle’s syndrome, results predominantly from
mutations in the C-termini of β
and γ-ENaC
subunits leading to a failure of Nedd4-2 (neuronal precursor
cell-expressed and developmentally down-regulated protein
4-2) mediated channel endocytosis and an increased expression
of ENaC at the cell surface.
The role of ENaC subunit polymorphisms as determinants of
essential hypertension has been investigated in a number of
studies. The T594M mutation in the β-subunit
of ENaC, for example, has been screened in large study populations
and there is conflicting evidence that it co-segregates with
blood pressure. Reasons for such controversies are discussed.
The authors conclude that ENaC is a pivotal convergence point
in blood pressure regulation and that future studies must
identify better ways to measure distal tubular ENaC activity
and investigate the importance of combination polymorphisms
of ENaC subunits and their regulatory proteins as genetic
determinants of hypertension.
[Back to top]
Concerning Arterial Hypertension, Homocysteine and
Paraoxonase-1
F. Rodríguez-Esparragón, A. Caballero-Hidalgo,
Y. Hernández Trujillo, A. Macías-Reyes and J.C.
Rodríguez-Pérez
[Full
text article]
An increased concentration of homocysteine (Hcy) is considered
an independent and graded cardiovascular risk factor. Hcy
can be non-specifically activated by methionyl-tRNA synthetase
to Homocysteine thiolactone (HTL). HTL is hydrolyzed to Hcy
by the paraoxonase/Thiolactonase (PON1) enzyme. PON1 is a
calcium-dependent esterase synthesized in the liver and contained
in plasma High-Density Lipoproteins (HDLs). The PON1 gene
is polymorphic. High thiolactonase activity was associated
with L55 and R192 alleles, whereas low thiolactonase activity
was associated with M55 and Q192 alleles. This study provides
a brief overview of some of the mechanisms by which Hcy affects
vascular function and the evidence that accounts for their
relevance in hypertension. The hypothesis by which alleles
encoding high thiolactonase forms of PON1 might confer vascular
protection under certain environmental conditions is discussed.
We also evaluated these alleles and conditions in patients
and controls from our institutional records.
[Back to top]
Hypertension in Children After Renal Transplantation
Tomáš Seeman
[Full
text article]
Hypertension is a serious complication in children after renal
transplantation, it is an important risk factor not only for
graft loss but also for cardiovascular morbidity and mortality
of transplanted patients. The etiology of posttransplant hypertension
is multifactorial - pretransplant hypertension, damaged native
kidneys, immunosuppressive therapy (steroids, cyclosporine,
tacrolimus), renal graft artery stenosis and chronic allograft
nephropathy are the most common causes. Ambulatory blood pressure
monitoring (ABPM) is the best method for blood pressure (BP)
evaluation in children after renal transplantation, it often
discloses especially night-time hypertension. The prevalence
of posttransplant hypertension ranges between 60-90% depending
on the method of BP measurement and definition of hypertension.
Left ventricular hypertrophy (LVH) is a frequent end-organ
damage in hypertensive children after renal transplantation
occurring in 50-80% of them. All classes of antihypertensive
drugs are used in the treatment of posttransplant hypertension,
it has never been proven that one class would be better than
another in BP lowering effects or in slowing the progressive
loss of graft function associated with chronic allograft nephropathy.
Control of hypertension in transplanted children is poor -
only 20-50% of treated children have normal BP. The reason
for this poor BP control seems to be an inadequate anti-hypertensive
therapy rather than a true resistance of posttransplant hypertension.
The unsatisfactorily low control of hypertension can be improved
by increasing the number of antihypertensive drugs, especially
of angiotensin converting enzyme inhibitors and diuretics.
Reduction or elimination of steroids, cyclosporine or tacrolimus
is able to reduce BP in transplanted children, however, it
could be associated with a risk of acute rejection. Nephrectomy
of the diseased native kidneys also decreases BP in transplanted
patients but it is performed very rarely in children. There
is still a great potential for improvement of antihypertensive
treatment that could result in improvement of both graft as
well as patient survival in children after renal transplantation.
[Back to top]
Pathophysiology of Hypertension During Preeclampsia:
Role of Inflammatory Cytokines
Babbette D. LaMarca, Michael J. Ryan and Joey P. Granger
[Full
text article]
Preeclampsia is defined as new onset hypertension with proteinuria
during pregnancy. The initiating event in preeclampsia is
postulated to be reduced uteroplacental perfusion which leads
to widespread dysfunction of the maternal vascular endothelium.
Inflammatory cytokines such as interleukin-6 (IL-6) and tumor
necrosis factor-alpha (TNF alpha) are thought to be important
links between placental ischemia and cardiovascular and renal
dysfunction. Supporting a potential role of cytokines in preeclampsia
are findings that plasma levels of TNF and IL-6 are elevated
in women with pree-clampsia. Important blood pressure regulatory
systems such as the renin-angiotensin system, sympathetic
nervous system, and endothelial factors interact with pro-inflammatory
cytokines such as IL-6 and TNF. Pro-inflammatory cytokines
also affect vascular function and endothelium-derived factors
involved in blood pressure regulation. Thus, endothelial dysfunction
associated with preeclampsia may be mediated by cytokines.
Recent studies have indicated that chronic reductions in placental
perfusion in pregnant animals are associated with enhanced
production of inflammatory cytokines, such as TNF alpha and
IL-6. In addition, chronic infusion of either TNF alpha or
IL-6 into normal pregnant rats results in significant increases
in arterial pressure and a decrease in renal hemodynamics.
TNF alpha activates the endothelin system in placenta, renal
and vascular tissues whereas IL-6 stimulates the renin-angiotensin
system. Collectively, these findings suggest that inflammatory
cytokines play a role in causing hypertension in response
to chronic reductions in uterine perfusion during pregnancy
by activating multiple neurohumoral and endothelial factors.
[Back to top]
Heme Oxygenase-1: A Potential Antihypertensive Target?
Trinity Vera and David E. Stec
[Full
text article]
The heme oxygenase (HO) system has received significant
attention in recent years as a possible novel target for antihypertensive
therapy. HO is the rate limiting enzyme in the metabolism
of heme releasing bioactive molecules carbon monoxide (CO)
and bilirubin each with beneficial cardiovascular actions.
Induction of HO-1 has been demonstrated to lower blood pressure
in several animal models of hypertension In addition to its
blood pressure lowering effects, HO can also reduce target
organ injury and protect against ischemic injury. Growing
experimental evidence suggests that increases in either CO
or bilirubin alone may also lower blood pressure and provide
protection against hypertensive and ischemic end-organ damage.
In this review, we will discuss the current understanding
of the actions of the HO on the kidney and cardiovascular
systems and how the HO system or its products may be manipulated
for antihypertensive therapy.
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