Current Hypertension
Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 4, Number 3, August 2008
Contents
Pulmonary Hypertension in the Critically Ill
Pp. 150-160
Michelle S. Chew, Lill Bergenzaun, Hans
Öhlin and Anders Ersson
[Abstract]
Role of WNK Kinases in Blood Pressure Control
Pp. 161-166
Sung-Sen Yang, Shih-Hua Lin and
Chou-Long Huang
[Abstract]
A Comparative Literature Review Exploring Hypertension
Drugs that Lower Target Organ Damage Above and Beyond Reducing
Blood Pressure Based on Research Studies Between 1992 and
2006 Pp. 167-176
Ehte Bahiru and Robert A. Kloner
[Abstract]
Emerging Roles for Connexins in Hypertension
Pp. 177-182
S. Carballo, A. Pfenniger, D. Carballo, A. Perrier,
F. Mach and B.R. Kwak
[Abstract]
Five Markers Capable to Identify Passive Smoking
Exposure Associated with Endothelial Dysfunction in Healthy
Individuals Pp. 183-189
Aurelio Leone
[Abstract]
Role of ERK1/2 Activation In Thrombin-Induced Vascular
Smooth Muscle Cell Hypertrophy Pp. 190-196
Esma R. Isenovic, Andreja Trpkovic, Zorica Zakula, Goran
Koricanac and Pierre Marche
[Abstract]
The Roles of Abnormal Renal Sodium Handling in
Hypertension Associated with Metabolic Syndrome Pp.
197-202
George Seki, Hideomi Yamada, Yuehong Li,
Shoko Horita, Masashi Suzuki and Toshiro Fujita
[Abstract]
The Reservoir-Wave Paradigm: Potential Implications
for Hypertension Pp. 203-213
John V. Tyberg,Nigel G. Shrive, J. Christopher
Bouwmeester, Kim H. Parker and Jiun-Jr Wang
[Abstract]
Blood Pressure Management in Metabolic Syndrome
Pp. 214-226
Yuichiro Yano, Satoshi Hoshide, Kazuyuki Shimada and
Kazuomi Kario
[Abstract]
Abstracts
[Back to top]
Pulmonary Hypertension in the Critically Ill
Michelle S. Chew, Lill Bergenzaun, Hans
Öhlin and Anders Ersson
Pulmonary hypertension is not uncommonly seen in the
critically ill. It may be encountered in patients with pre-existing
diseases or may occur acutely without predisposing conditions.
The diagnosis and management of pulmonary hypertension can
be very challenging, given that critically ill patients are
often concurrently haemodynamically unstable. Commonly used
therapies in the Intensive Care Unit, such as fluid resuscitation,
mechanical ventilation, vasopressors and inotropes may have
deleterious effects in this population. We review the pathophysiology,
diagnosis and current management strategies of this disease,
with special emphasis on the critically ill adult population.
[Back to top]
Role of WNK Kinases in Blood Pressure Control
Sung-Sen Yang, Shih-Hua Lin and Chou-Long
Huang
With-No-Lysine [K] (WNK) kinases
are a group of serine/threonine protein kinases with an unusual
location of the catalytic lysine. There are four mammalian
WNK kinases, WNK1-4, each encoded by a separate gene. In addition,
WNK1 has two alternatively spliced isoforms: a ubiquitously
expressed full-length long isoform (L-WNK1) with kinase activity
and a kidney-specific isoform (KS-WNK1) lacking kinase activity.
Mutations of WNK1 and WNK4 genes cause a
genetic hypertension syndrome, pseudohypoaldosteronism type
2 (PHA2). Recent studies show that WNK1, 3 and 4 are expressed
in the aldosterone-sensitive distal tubules of kidney and
contribute to sodium (Na+) and potassium (K+)
homeostasis by regulating tubular Na+ and K+
transporters in complex manners. Mice with heterozygous disruption
of WNK1 gene have hypotension but without apparent
renal Na+ wasting. L-WNK1 is also expressed in
heart and blood vessel. Thus, function of WNK1 in cardiovascular
system may also contribute to blood pressure regulation. Transgenic
or knockin mice carrying a disease-causing WNK4 gene
exhibit typical phenotypes of PHA2 by increasing renal Na+
reabsorption. The review summarizes recent studies on the
mechanism of WNK kinases regulation of Na+ homeostasis
and cardiovascular function and the role in blood pressure
control.
[Back to top]
A Comparative Literature Review Exploring Hypertension
Drugs that Lower Target Organ Damage Above and Beyond Reducing
Blood Pressure Based on Research Studies Between 1992 and
2006
Ehte Bahiru and Robert A. Kloner
Approximately 65 million individuals in the United States
suffer from systemic hypertension. Hypertension leads to various
cardiovascular diseases including myocardial infarction, stroke,
kidney disease, and others. Hypertension is commonly linked
to other risk factors for cardiovascular diseases such as
diabetes, dyslipidemia, and smoking. For this study, we reviewed
24 recently published papers that compared different hypertension
drugs with other drugs or placebo in their effectiveness to
reduce blood pressure and major primary end points. We hypothesized
that some drugs reduce the primary end point above and beyond
simply reducing the blood pressure. We categorized papers
into a number of groups to determine how many papers showed
that drug vs. placebo or one drug regimen versus
another drug regimen could better reduce a primary clinical
end point independent of a better reduction in blood pressure.
We found four papers that showed a benefit of a pharmacological
regimen on major clinical end points above and beyond reduction
of blood pressure. These findings primarily involve drugs
that affect the renin-angiotensin-aldosterone system.
[Back to top]
Emerging Roles for Connexins in Hypertension
S. Carballo, A. Pfenniger, D. Carballo, A. Perrier,
F. Mach and B.R. Kwak
The current pharmacological arsenal for treating hypertension
includes diuretics, inhibition of the Renin-Angiotensin-Aldosterone
(RAA) cascade and alpha blockade, often with inadequate results.
Gap junction proteins, connexins (Cx), are ubiquitously expressed
in organs involved in the pathogenesis of hypertension, namely
brain, heart, vascular bed and kidney. Central to hypertension
is increased vasomotor tone, itself determined by both paracrine
mediators as well as by cell-cell interaction mediated by
connexins. Four connexins are involved (Cx37, Cx40, Cx43 and
Cx45); their expression patterns and function differ both
in physiological conditions as well as in disease states such
as hypertension and atherosclerosis. Cx37, Cx40 and Cx43 are
expressed in endothelial cells, whereas Cx43 and Cx45 are
mostly expressed in vascular smooth muscle cells. Animal models
demonstrate a distinct role of Cx40 and Cx43 in renal hypertension.
Furthermore, Cx40-deficient mice are constitutively hypertensive
and a polymorphism in the promoter region of the encoding
gene is associated with an increased risk of hypertension
in humans; both observations imply an independent pathophysiological
mechanism for the development of hypertension. Whether modifications
of function and expression of connexins are markers or causative
for disease remains to be determined. However, modulation
of connexin-mediated communication may represent a novel therapeutic
approach for hypertension.
[Back to top]
Five Markers Capable to Identify Passive Smoking Exposure
Associated with Endothelial Dysfunction in Healthy Individuals
Aurelio Leone
By the analysis of our previous studies, functional and
biochemical markers related to ETS exposure are discussed.
18 healthy never smokers, 12 men (67%), 6 women (33%), 21
to 55 years old (mean:34+/-9 ys.) underwent twice - in a smoking
free environment and in the same environment polluted by 35
ppm carbon monoxide from cigarette smoking brachial artery
ultrasonography, exercise stress testing, heart rate (HR)
and blood pressure (BP) monitoring, carboxy-hemoglobin (COHb)
dosage. In ETS exposure compared with no exposure, flow-mediated
dilation mean value (FMD), assessed by ultrasonography, was
6.8+/-7.8% versus 12.6+/- 7.8%, significantly impaired; mean
HR was 89+ -4 beats/minute-for 2h duration- versus 77+/-4
beats/minute; systolic BP was 134+/-17 mmHg versus 124+/-21
mmHg; diastolic BP was 79+/-4 mmHg vs 76+/-5 mmHg,
with no change. Bicycle exercise stress testing showed a significantly
increase in mean time to recovery baseline parameters, 19.04+/-4
minutes versus 8.5 +/-4 minutes (P less than 0.01),and mean
COHb was 1.7+/-0.4% vs 0.8+/- 0.4 (P less than 0.01).
From the results observed, five markers of ETS exposure could
be identified and, then, discussed:1. Impaired FMD, effect
of endothelial dysfunction, 2. Transient increase in systolic
BP; 3. HR increase; 4.Diminished tolerance to exercise; 5.
Increased COHb blood concentrations.
[Back to top]
Role of ERK1/2 Activation In Thrombin-Induced Vascular
Smooth Muscle Cell Hypertrophy
Esma R. Isenovic, Andreja Trpkovic, Zorica Zakula, Goran
Koricanac and Pierre Marche
It is well recognized that the proliferation of vascular
smooth muscle cells (VSMCs) is a key event in the pathogenesis
of various vascular diseases, including atherosclerosis and
hypertension. It is generally considered that the phosphorylation/dephosphorylation
reactions of a variety of enzymes belonging to the family
of mitogen-activated protein kinases (MAPKs) play an important
role in the transduction of mitogenic signal. We have previously
shown that among extracellular signal-regulated protein kinases
(ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in
the cellular mitogenic machinery triggered by several VSMCs
activators, including thrombin. ERK1/2 activation by G-protein-coupled
receptors (GPCRs) has been shown to be Ca2+-dependent
and to require the transactivation of epidermal growth factor
receptor (EGFR). In addition, it is generally admitted that
variations of the intracellular Ca2+
concentration ([Ca2+] i)
play an important role in the transduction of mitogenic signal.
Recently, we have shown that in thrombin-stimulated VSMCs,
EGFR-independent activation of ERK1/2 activation could occur
when agonist-induced ([Ca2+]
i) elevation was reduced. This review examines recent findings
in ERK1/2 signaling pathway that have been identified as critically
important mediator of VSMCs hypertrophy and vascular diseases.
Future investigations should now focus on the mechanisms of
MAPK activation which might therefore represent a new mechanism
involved in the antiproliferative effect revealed in this
review.
[Back to top]
The Roles of Abnormal Renal Sodium Handling in Hypertension
Associated with Metabolic Syndrome
George Seki, Hideomi Yamada, Yuehong Li,
Shoko Horita, Masashi Suzuki and Toshiro Fujita
There is an epidemic of the metabolic syndrome across
the world, which is often associated with hypertension and
other coronary risk factors. Insulin resistance is thought
to play a key role in this condition. Several different mechanisms
such as activation of renin-angiotensin system, enhancement
of sympathetic nerve system, and hyperinsulinemia may underlie
hypertension in metabolic syndrome. Unlike in other tissues,
angiotensin II regulates renal proximal tubule transport in
a biphasic manner. The molecular mechanism for the angiotensin
II-mediated regulation of renal proximal transport has been
recently clarified. On the other hand, insulin stimulates
sodium transport in several nephron segments including proximal
tubules. Recent data have shown that the sodium-retaining
effect of insulin is paradoxically preserved in a mouse model
of insulin resistance, which may be enhanced by sympathetic
nerve activation. In this review, we will focus on the roles
of abnormal renal proximal tubule sodium handling in hypertension.
[Back to top]
The Reservoir-Wave Paradigm: Potential Implications
for Hypertension
John V. Tyberg,Nigel G. Shrive, J. Christopher
Bouwmeester, Kim H. Parker and Jiun-Jr Wang
Consistent with a straightforward, time-domain interpretation
of Westerhof’s classic circuit diagram of the 3-element
Windkessel, we have concluded that measured aortic pressure
is the instantaneous sum of a constant (P∞),
a Windkessel/reservoir pressure, and a wave-related pressure.
According to our interpretation, the resistive element interposed
between the left ventricle and the resistance-capacitance
(RC) filter is, in fact, a hydraulic resistance in the proximal
aorta that defines the wave-related pressure. The RC filter
subserves the Windkessel/reservoir function and is distributed
anatomically within the large arteries. The lower potential
(pressure) of the RC filter (P∞)
is not zero or even venous or mean circulatory pressure, but
rather a higher pressure (~30–40 mmHg) toward which
aortic pressure declines asymptotically during diastole. As
previously recognized, the Windkessel/reservoir pressure describes
aortic diastolic pressure very precisely; in the new paradigm,
the addition of the wave-related pressure provides the complement
that describes systolic pressure equally precisely.
This new interpretation has several potential implications
for our understanding of hypertension. Diastolic hypertension
would seem to be related most directly to alterations in reservoir
pressure, particularly P∞
and reservoir resistance. Systolic hypertension may be a function
of several factors: wave reflection, increased proximal aortic
resistance, and decreased aortic compliance.
[Back to top]
Blood Pressure Management in Metabolic Syndrome
Yuichiro Yano, Satoshi Hoshide, Kazuyuki
Shimada and Kazuomi Kario
To assess 24-hour BP levels in subjects with metabolic syndrome
is essential, because hypertension, which is the most prevalent
component in the syndrome, makes the major contribution to
cardiovascular risk. Because BP levels in subjects with metabolic
syndrome are prone to be elevated in an out-of-office setting
(i.e., nocturnal hypertension, morning hypertension), measurement
of home and/or ambulatory BP levels is a promising method
for managing the syndrome. The best treatment approach for
this complex condition is a multifactorial one, much emphasis
has been placed on RAAS inhibition, which is one of the most
important factors in the disease, although there has been
no clear evidence that RAAS inhibitors are more effective
than other drugs for treatment of metabolic syndrome. However,
previous trials for treating hypertension have generally enrolled
non-obese patients, and have enrolled more complicated high-risk
patients, in whom the most important issue is BP lowering
itself. here is thus a need to assess how to treat relatively
younger subjects with-milder and/or high-normal hypertension,
because the prevalence of such patients is expected to increase
dramatically along with burgeoning obesity rates.
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