Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 2, Number 4, November 2006
Contents
Renal Ischemia: How Commonly Does it Cause Renal Failure?
Pp. 255-261
Renee Dua, Mitra K. Nadim, Jerry Soung and Vito M. Campese
[Abstract]
Perivascular Inflammation and Hypertensive Cardiovascular
Remodeling Pp. 263-269
Hisashi Kai, Fumitaka Kuwahara, Keisuke Tokuda and Tsutomu
Imaizumi
[Abstract]
Isolated Systolic Hypertension: Epidemiology, Pathogenesis
and Treatment Pp. 271-274
Danny Dvir, Yehonatan Sharabi and Ehud Grossman
[Abstract]
Context-Dependency of Relations Between Cardiovascular
Phenotypes and Genes Involved in Sodium Homeostasis: Findings
from the European Project on Genes in Hypertension
Pp. 275-281
Tatiana Kuznetsova, Jan A. Staessen, Eva Brand, Marcin
Cwynar, Katarzyna Stolarz, Lutgarde Thijs, Valérie
Tikhonoff, Wiktoria Wojciechowska, Speranta Babeanu, Stefan-Martin
Brand-Herrmann, Edoardo Casiglia, Jan Filipovský, Tomasz
Grodzicki, Yuri Nikitin, Jan Peleška, Harry Struijker-Boudier,
Giuseppe Bianchi and Kalina Kawecka-Jaszcz
[Abstract]
Roles of Adrenomedullin in Hypertension and
Hypertensive Organ Damage Pp. 283-295
Johji Kato, Kazuo Kitamura and Tanenao Eto
[Abstract]
Sympathetic Overactivity in Patients with Chronic
Renal Failure – The Culprit of Increased Cardiovascular
Mortality? Pp. 297-300
Martin Hausberg, Uta Hillebrandt, Detlef Lang, Andrea
Levers and Markus Kosch
[Abstract]
Benign Prostatic Hyperplasia and Clinical Prostate
Cancer – Two New Components of the Metabolic Syndrome
Pp. 301-309
Hammarsten Jan
[Abstract]
Role of Renin-Angiotensin System in Vascular
Endothelial Dysfunction of Pregnancy-Induced Hypertension
Pp. 311-316
Keiichi Matsubara, Yuko Matsubara and Masaharu Ito
[Abstract]
Pre-eclampsia Versus Cardiovascular
Disease Versus CRP Pp. 317-323
Luís Belo, Alice Santos-Silva, Alexandre Quintanilha
and Irene Rebelo
[Abstract]
Pathophysiological Roles of Renin-Angiotensin
System on Erythropoietic Action Pp. 325-331
Hideki Kato, Masaomi Nangaku, Akiyoshi Fukamizu and Toshiro
Fujita
[Abstract]
Abstracts
[Back to top]
Renal Ischemia: How Commonly Does it Cause Renal Failure?
Renee Dua, Mitra K. Nadim, Jerry Soung and Vito M. Campese
The prevalence of chronic kidney disease (CKD) and end-stage
renal disease (ESRD) are steadily increasing. This phenomenon
is in part linked to the aging of the US population, in part
to the increasing prevalence of obesity, diabetes and related
renal diseases. Some believe that renal ischemia may be a
frequent cause of CKD and ESRD, but the prevalence of this
condition is difficult to ascertain due to limitations of
available diagnostic tools.
The current definition of renal ischemia is also ground for
confusion. Renal ischemia as a cause of progressive renal
disease is commonly defined as a progressive decrease in glomerular
filtration rate due to atherosclerosis of the main renal arteries.
This definition however, is too restrictive and it does not
take into account that functional and anatomical alterations
of the renal microcirculation may also lead to progressive
renal failure.
In this review, we evaluate the clinical and pathophysiological
aspects of ischemia-related progressive kidney disease.
[Back to top]
Perivascular Inflammation and Hypertensive Cardiovascular
Remodeling
Hisashi Kai, Fumitaka Kuwahara, Keisuke Tokuda and Tsutomu
Imaizumi
Myocardial fibrosis has drawn an attention as the pathogenesis
of impaired diastolic function in hypertensive hearts. However,
the mechanisms whereby hypertension provokes myocardial fibrosis
are not fully understood. Recently, we have demonstrated that
Wistar rat with a suprarenal aortic constriction is a model
of cardiac hypertrophy associated with preserved systolic,
but impaired diastolic function. In this model, a rapid blood
pressure rise provokes transient upregulations of intercellular
adhesion molecule-1 (ICAM-1) and monocyte chemoattractant
factor-1 (MCP-1) in the intramyocardial arteries, which in
turn trigger perivascular macrophage infiltration. Following
the inflammatory changes, myocardial fibrosis extends from
perivascular to intermuscular interstitial spaces, which resulting
in typical feature of reactive fibrosis. MCP-1 function blocking
not only inhibits macrophage infiltration but also prevents
reactive fibrosis and diastolic dysfunction, while not affecting
blood pressure, myocyte hypertrophy, and systolic function.
Tissue angiotensin system is a possible activator of perivascular
inflammation. Accordingly, a substantial role of inflammation
is suggested in myocardial fibrosis and diastolic dysfunction
in hypertensive hearts. Targeting inflammation may be a new
strategy for prevention and treatment of myocardial fibrosis
and diastolic dysfunction in hypertensive hearts.
[Back to top]
Isolated Systolic Hypertension: Epidemiology, Pathogenesis
and Treatment
Danny Dvir, Yehonatan Sharabi and Ehud Grossman
Isolated systolic hypertension (ISHTN) is rapidly rising
in prevalence, largely due to the advancing age of the population
and it will soon become the most common type of hypertension.
Untreated patients with merely borderline ISHTN already have
a 50% grater risk for cardiovascular complications. Several
studies demonstrated that treating ISHTN is beneficial. However,
such treatment could cause a potential harm by further reducing
the non-elevated diastolic blood pressure; a theory that underlies
the controversial “J curve”. In this review, we
summarize the epidemiology and pathogenesis of this disorder
according to the latest studies, with special emphasis on
when, and to what goal, blood pressure should be lowered,
and with which medications.
[Back to top]
Context-Dependency of Relations Between Cardiovascular
Phenotypes and Genes Involved in Sodium Homeostasis: Findings
from the European Project on Genes in Hypertension
Tatiana Kuznetsova, Jan A. Staessen, Eva Brand, Marcin
Cwynar, Katarzyna Stolarz, Lutgarde Thijs, Valérie
Tikhonoff, Wiktoria Wojciechowska, Speranta Babeanu, Stefan-Martin
Brand-Herrmann, Edoardo Casiglia, Jan Filipovský, Tomasz
Grodzicki, Yuri Nikitin, Jan Peleška, Harry Struijker-Boudier,
Giuseppe Bianchi and Kalina Kawecka-Jaszcz
Hypertension is a chronic age-related disorder, affecting
nearly 20% of all adult Europeans. This disease entails debilitating
cardiovascular complications and is the leading cause for
drug prescriptions in Europeans older then 50 years. Intensive
research over the past two decades failed so far to identify
common genetic polymorphisms with major impact on blood pressure
or associated cardiovascular phenotypes, suggesting that multiple
genes each with a minor impact, along with gene-gene and gene-environment
interactions play a role. The European Project on Genes in
Hypertension (EPOGH) is a large-scale family-based study,
in which participants from 7 different populations were phenotyped
and genotyped according to standardised procedures. This review
article summarizes the initial 5 year findings and puts these
observations into perspective against other published studies.
EPOGH demonstrated that phenotype-genotype relations strongly
depend on host factors, such as gender and lifestyle, in particular
salt intake as reflected by the 24 hour urinary excretion
of sodium. EPOGH therefore highlights the concept that phenotype-genotype
relations can only be studied within a defined ecogenetic
context.
[Back to top]
Roles of Adrenomedullin in Hypertension and
Hypertensive Organ Damage
Johji Kato, Kazuo Kitamura and Tanenao Eto
Adrenomedullin (AM) is a bioactive peptide having a wide range
of biological actions such as vasodilatation, natriuresis,
diuresis and inhibition of aldosterone secretion. Various
organs and tissues, including the myocardium, vascular wall
and kidneys, produce AM, and AM is also present in the bloodstream.
Plasma levels of AM were elevated in patients with essential
or secondary hypertension as compared with normotensive controls.
When infused in a relatively short period of time, AM reduced
blood pressure in humans and experimental animals largely
through vasodilatation. The blood pressure of transgenic mice
overexpressing AM was lower than that of their wild-type littermates;
while heterozygotes of AM knockout mice showed higher blood
pressure, suggesting a role for endogenous AM in the regulation
of blood pressure. Studies with cultured cardiac cells suggest
a role for AM in inhibiting hypertrophy or fibrosis of the
heart as an autocrine or paracrine factor. Animal experiment
studies showed that either prolonged infusion or virally mediated
overexpression of AM ameliorated the cardiovascular and renal
damage associated with hypertension. Thus, a body of evidence
accumulated in this field suggests that AM functions to counteract
the elevation in blood pressure and progression of hypertensive
organ damage.
[Back to top]
Sympathetic Overactivity in Patients with Chronic
Renal Failure – The Culprit of Increased Cardiovascular
Mortality?
Martin Hausberg, Uta Hillebrandt, Detlef Lang, Andrea
Levers and Markus Kosch
Tonic activation of the sympathetic nervous system is
a major factor contributing to hypertension in patients with
chronic renal failure. Besides its role in blood pressure
regulation, sympathetic overactivity causes structural and
functional alterations of the myocardium and large artery
walls. Altogether, these factors contribute substantially
to the increased cardiovascular morbidity and mortality in
patients with chronic renal disease. Moreover, increased sympathetic
outflow in conjunction with increased oxidative stress causes
progression of renal disease thereby accelerating the course
towards the need of renal replacement therapy.
The origin of increased sympathetic outflow in patients with
renal disease still has not been fully elucidated. There is
sound evidence that signals arising from the diseased kidneys
– mediated via renal afferent nerves –
cause tonic activation of efferent sympathetic nerve fibres.
Renal ischemia with release of adenosine and renal chemoreceptor
activation, accumulation of angiotensin II and fibroproliferative
scarring with renal mechanoreceptor dysfunction may be involved
in the activation of renal afferences.
Sympathetic overactivity in renal disease can be diminished
by blockers of the renin angiotensin aldosterone system, by
adrenoreceptor blockers and by substances inhibiting central
sympathetic outflow such as imidazolines. These drugs not
only reduce sympathetic nerve activity, they attenuate cardiovascular
pathology and they slow the progression of renal disease.
A combination of these drugs in patients with chronic renal
failure seems promising and warrants randomized large-scale
studies.
[Back to top]
Benign Prostatic Hyperplasia and Clinical Prostate
Cancer – Two New Components of the Metabolic Syndrome
Hammarsten Jan
The metabolic syndrome is a common generator of diseases
in countries with western civilization lifestyles. Type 2
diabetes, atherosclerotic disease manifestations, hypertension,
obesity, dyslipidaemia, hyperuricaemia, hyperinsulinaemia,
dysfibrinolysis and microalbuminuria are considered to be
established components of the metabolic syndrome. A clinical
observation that obese and/or diabetic men appeared to have
a greater prostate gland than men without these conditions
generated a series of scientific investigations. An important
finding was that benign prostatic hyperplasia (BPH), as measured
by the total prostate gland volume or the annual BPH growth
rate, was statistically associated with 17 out of 19 components
of the metabolic syndrome. Another important finding was that
clinical prostate cancer, as measured by stage, grade and
PSA-value, was linked to seven of nine components of the metabolic
syndrome. Furthermore, it was found that lethal clinical prostate
cancer was associated with six (and two more with borderline
statistical significance) of ten components of the metabolic
syndrome. Still another important finding was that fasting
plasma insulin was independently associated with both BPH
and clinical prostate cancer. In conclusion, the results of
these studies indicate that there is an association between
the metabolic syndrome and two important urological tumors,
namely BPH and clinical prostate cancer. The results also
indicate that BPH and clinical prostate cancer may be regarded
as two new components of the metabolic syndrome besides Type
2 diabetes, hypertension, atherosclerotic disease manifestations,
obesity, dyslipidaemia and others. The studies also suggest
that fasting plasma insulin is a promoter of both BPH and
clinical prostate cancer. The results have generated the hypothesis
that hyperinsulinaemia is a primary event in the development
of both BPH and clinical prostate cancer. If the results can
be confirmed in future studies, they would give rise to very
significant practical implications in the medical care sector.
This article is essentially a review of the findings of our
research group over the last 15 years on the link between
hyperinsulinaemia and related metabolic perturbations.
[Back to top]
Role of Renin-Angiotensin System in Vascular
Endothelial Dysfunction of Pregnancy-Induced Hypertension
Keiichi Matsubara, Yuko Matsubara and Masaharu Ito
During pregnancy, the renin-angiotensin system (RAS)
plays an important role in regulating the markedly expanded
circulating blood volume in the uteroplacental circulation.
RAS is activated during normal pregnancy; however, blood pressure
decreases from the 1st trimester to the 2nd trimester. Vascular
responsiveness to angiotensin II (AngII) decreases early in
pregnancy; on the other hand, pregnant women who subsequently
develop PIH are exquisitely sensitive to the pressor effect
of AngII. Interestingly. the maternal circulating RAS and
the placental concentration of AngII receptor (ATR) are stable
or reduced in PIH. The balance of expression between ATR subtype
1 (AT1) and 2 (AT2) is potentially important in the regulation
of vascular tone during pregnancy. Increased AT1/AT2 may explain
the loss of vascular refractoriness to AngII in the pathogenesis
of PIH.
Recently, endothelial progenitor cell (EPC) has been found
in the peripheral blood of pregnant women. Although AngII
stimulates EPC proliferation, the mobilization is inhibited
in PIH. Impairment of EPC mobilization may contribute to insufficient
regeneration of endothelium in the impaired utero-placental
circulation of PIH.
This review focuses on vascular endothelial dysfunction and
the effect of RAS in the pathophysiology of PIH.
[Back to top]
Pre-eclampsia Versus Cardiovascular
Disease Versus CRP
Luís Belo, Alice Santos-Silva, Alexandre Quintanilha
and Irene Rebelo
Pre-eclampsia (PE), a hypertensive disorder of human
pregnancy, shares some similarities with atherosclerosis and
some studies support the theory that PE may work as a marker
of increased cardiovascular risk later in life. Atherosclerosis
is an inflammatory disease and raised C-reactive protein (CRP)
levels have emerged as a powerful marker in predicting cardiovascular
events. PE may represent an exacerbated form of inflammation
compared with normal pregnancies; actually, a large number
of studies have reported higher CRP levels in women with established
PE. This paper reviews the association of elevated CRP levels
with the development of PE and with the development of cardiovascular
disease later in life. The need of studies evaluating CRP,
as well as other novel cardiovascular risk factors, in non-pregnant
women with a history of PE is highlighted, and attention is
given to the potential preventive strategies to reduce cardiovascular
risk in such women.
[Back to top]
Pathophysiological Roles of Renin-Angiotensin
System on Erythropoietic Action
Hideki Kato, Masaomi Nangaku, Akiyoshi Fukamizu and Toshiro
Fujita
The renin-angiotensin system (RAS) has been known to
exert various actions on diverse target tissues such as kidney,
heart, vascular system, and brain as well as blood pressure
regulation and fluid homeostasis. In addition, various animal
experiments and clinical studies suggested a role of RAS on
the erythropoiesis. In RAS activated clinical situations such
as posttransplant erythrocytosis, renin secreting tumors,
and renal artery stenosis, positive erythropoiesis has been
suggested. In contrast, by use of anti-RAS drugs such as angiotensin
converting enzyme inhibitors or angiotensin II type 1 receptor
blockers, negative erythropoiesis has been also reported in
RAS inhibited situations. In this era of genetically engineered
mice available, transgenic and knockout mice of RAS components
have been conspicuously analyzed and these animals definitely
revealed positive and negative regulation of erythropoiesis
by RAS in vivo. The primary mechanism of enhanced
erythropoiesis by RAS activation is increased erythropoietin
production via angiotensin II type 1 receptor. A
mechanism of progression of anemia by RAS inhibition is less
clear. While a slight decrease of hemoglobin is observed in
association with the use anti-RAS drugs in clinical situations,
other beneficial effects of these reagents apparently validate
application of these reagents to patients.
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