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High Blood Pressure Research Council of Australia |
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HBPRCA
Quarterly Email Newsletter
March
2006
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This is the first HBPRCA e-news for
the year as we will be making them quarterly rather than every month. So
expect the next one in June. The less frequent newsletters may mean that we
send the occasional email to members as urgent issues arise but we will try
to keep these to a minimum. The major focus of the executive at the moment
has been in preparing for the ASM in Brisbane, which promises to be once
again a major event. While our opening ceremony won’t quite rival the
Commonwealth Games, you can be assured that Jaye and her team will be working
tirelessly to bring about another spectacular meeting. On that note we will
be planning to hold as the meeting workshop, a telemetry users group one day
meeting on the Wednesday (see below).
Our feature article this time is from the Baker Heart Research
Institute and is the first of 2 parts. Don’t forget that the ISH abstract deadline is fast
approaching. ISH Abstract Submission
Deadline: April 15, 2006 |
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PRESIDENT’S MESSAGE from Stephen Harrap Welcome back to eNews for 2006.
Your busy Executive has been meeting and planning for the New Year already. A
major goal is to make the Brisbane Annual Scientific Meeting a conference to
remember. You'll find more news on developments elsewhere in eNews including
the formation of a local liaison committee in Brisbane and some exciting news
about our named lecturers. We are also taking the opportunity to use the
Brisbane meeting to augment our membership in Brisbane and attract some of
the real research talent in the Queensland capital. Lots more things will be
happening during 2006 to build on the achievements of 2005. We look forward
to keeping you up to date. |
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MEETING NEWS from Jaye Chin Dusting
To lift an excerpt from the American Hypertension site :-
"Friedrich Luft was born in 1942 in Berlin. However, he grew up in the
USA after his parents emigrated in 1947. He studied medicine at the Jefferson
Medical School in Philadelphia, PA, USA. He was Professor of Medicine and
Pharmacology at Indiana University School of Medicine until 1989. He then
came to Germany, first to the University of Erlangen but shortly thereafter
to Berlin-Buch. Luft has received numerous honors in the past, including the
Arthur Corcoran Award of the American Heart Association, the Ernest Starling
Award of the American Physiological Society, the Franz Gross Award of the
German Hypertension League, the Award of the Helmut and Ruth Lingen
Foundation (Cologne), as well as the Björn Folkow Prize of the European
Society for Hypertension. In 2002 he was elected as a member of the oldest
Academy of Natural Sciences in Germany, the Leopoldina. Prof Luft's career
has been dedicated to translating basic research into the treatment of
cardiovascular disease in humans, and particularly, to training
physician-scientists in cardiovascular research. He is responsible for a
research group at the affiliated Max Delbrück Center for Molecular Medicine
(MDC) Berlin-Buch." We have much to look forward to. |
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3rd
Australian Telemetry Users Group Meeting at the HBPRCA ASM As the official ASM workshop
this year we intend to hold a one day meeting sponsored by the suppliers of telemetry
equipment, Data Sciences International. The event will be on the Wednesday
the 6th of December in Brisbane prior to the ASM and is being
organised by Geoff Head and Dmitry Mayorov.
The last meeting was held in 2001 so there are many new developments since
that time. For those currently using the equipment or interested in its
potential, the workshop is an ideal time to get to know others in the area
and discuss the highs and lows of radiotelemetry (hopefully mostly highs).
Data Sciences will be sending representatives for us to engage in what is
usually a forthright discussion. |
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MEMBERSHIP
MESSAGE from
Doug McKitrick March 31st is the annual
subscription due date for the HBPRCA. If you have thus far overlooked paying
it’s still not too late! Simply go to the HBPRCA website and follow the
link on the left for access to the secure payment site or to download a form
for return by post. If you don’t have internet access, can’t remember if you
have paid, or just need a bit of help, contact the Secretariat by phone, fax
or post (details below). Don’t forget to encourage your
graduate students and post docs to take out membership with the Council. The
special initiatives that have been introduced are specifically intended to
benefit student and early career members.
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SOCIETY NEWS from Kate Denton The "Young Investigator Exchange" initiative with
the British Hypertension Society kicked off by Dr Carmel McEniery's visit at
our last annual meeting was a fantastic success. The British have taken up the challenge with enthusiasm and
plans are all ready in hand to make Enzo Porrello's visit not only enjoyable
but also productive. Laboratory
visits in the weeks preceding the meeting have all ready been arranged. This
is a marvellous chance for our "Young Investigators" starting out
in a career in research to start to build an international profile. We expect
the competition for this prize to increase as the worth of this opportunity
becomes recognised. On another front, negotiations with the American Council
for High Blood Pressure Research (CHBPR) are moving forward. Our proposal that travel awards given by
this society be opened to Australians have been meet with support from Robert
Carey (President, CHBPR). Our
proposal has been put on the agenda for the spring executive meeting of the
CHBPR. I have attended CHBPR meetings
and found them very worthwhile. Smaller than many American meetings there is
plenty of opportunity to interact with key people in the hypertension field
in the US. |
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As winner of the British Hypertension
Society Young Investigator Award in 2005, I was delighted to have the
opportunity to attend the HBPRCA Annual Scientific Meeting in Melbourne in
December to present some of my work. This initiative, established by Stephen
Harrap and Neil Poulter (BHS), aims to strengthen links between the two
societies, and provides an ideal opportunity for young investigators to meet
and interact with international colleagues working within the broad field of
hypertension. Being the inaugural recipient of this award, I did feel
somewhat of a human guinea pig. However, the meeting itself was a great
success, and the interactive and friendly atmosphere throughout, made for a
most enjoyable visit. Whilst in Melbourne, and as part of the exchange, I met
with Bronwyn Kingwell and her group at the Baker Institute. I later travelled
to Sydney to meet with an ongoing collaborator, Alberto Avolio (UNSW) and
then ended my stay in Brisbane (my home town originally!), where I was kindly
invited to present some more of my work to Michael Stowasser’s and Tom
Marwick’s groups (UQ). I would like to express my sincere thanks to Stephen
Harrap and Neil Poulter for initiating the exchange scheme, and Kate Denton
for her help with organizing the mechanics of my visit. I shall now look
forward to welcoming the HBPRCA Young Investigator Winner, Enzo Porello to
Cambridge for the BHS meeting next September. |
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MARCH FEATURE ARTICLE Cardiovascular Research at the Baker
Heart Research Institute – Part 1 |
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The Institute now consists of over 250 staff and students organised
into four major divisions which are; the Experimental
Cardiology and Heart Failure Division headed by David Kaye, the Atherothrombosis and Vascular Division headed by newly arrived from Germany, Dr.
Karheinz Peter, the JDRF Diabetes & Metabolism Division
headed by Professor Mark Cooper and the Cardiovascular
Neurosciences Division headed by
Professor Murray Esler. This newsletter is Part 1
from the Baker Institute and comprises some of the research areas related to
hypertension and cardiovascular disease. |
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Wynn Department of Metabolic Cardiology: Professor David KayeIn 2003, David Kaye was appointed as Head of the Wynn Department of
Metabolic Cardiology, which was established through a generous grant from the Atherosclerosis Research Trust of the United Kingdom. Some of Prof. Kaye’s recent research work
has been directed at exploring the role of impaired L-arginine transport in
the pathogenesis of endothelial dysfunction in disease states including
atherosclerosis, heart failure, diabetes and hypertension. |
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Wynn
Department of Metabolic Cardiology back row
from left to right: Rebecca Ritchie, David Kaye, Adam Bilney, Wei-Zheng Zang,
Zhiyong Yang, Anka Smolic, Charles Lang, front row left to right:Tanneale
Marshall, Anh Cao, Carla Enriquez, Abi Chong, Kylie Venardos, Laura Willems
Absent: Samara Finch (maternity leave) |
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Arginine studies
Samara Finch, David Kaye and Zhiyong Yang have been examining the molecular
basis for abnormal arginine transport in essential hypertension. Previously,
we had reported the identification of 13 single nucleotide polymorphisms
(SNPs) around the CAT1 gene. Among them, one SNP at 3’ untranslated region (UTR) was of great
interest in terms of its potential role in gene regulation in transcriptional
level, we therefore surveyed the allele
frequency of this SNP with DNA samples deposited in Baker-Alfred’s Gene Bank
Collection from people with or without hypertension. We found that 3’
UTR polymorphism may play a role in regulating CAT-1 gene expression, thus
regulating arginine transport. Zhiyong Yang is now developing a CAT1 transgenic mouse. Wei-Zheng Zhang has
found that a cigarette smoke extract is able to chemically modify active
molecules to affect endothelial arginine uptake and arginine metabolism
resulting in decreasing intracellular arginine bio-viability, reducing nitric
oxide production and increasing asymmetric dimethylarginine which
is a new risk factor for cardiovascular diseases. David Kaye and his team are identifying
novel modulators of arginine transport and have screened a library of 300
novel compounds for their ability to increase intracellular arginine
transport. In recent studies they found that some of the most promising
compounds lowered blood pressure.
Other projects include the role of oxidative stress, angiotensin
peptides and insulin in regulating arginine transport. A major undertaking has been determining
the relevance of arginine metabolism to patients with Coronary Artery Disease
by assaying samples from over 200 subjects. Chronic Heart Failure (CHF)
The other major focus of the laboratory is to understand the
neurobiological and metabolic mechanisms in heart failure. A characteristic
of heart failure is increased activity of the sympathetic nervous system
(SNS), presumably to compensate for a reduction in cardiac output and to
maintain tissue perfusion. Increased
SNS activity commonly results in excess norepinephrine remaining within the
myocardium. Tanneale
Marshall and David Kaye
are generating a recombinant adenovirus containing the norepinephrine
transporter (NET) gene. The aim of this study is to determine whether
expression of NET in cardiomyocytes can reduce the cardiotoxic affects of excess
NE associated with heart failure.
Little is known or documented about the mechanisms controlling NETs
trafficking to the cell membrane or the biochemical pathways it signals
through. We have been able to
demonstrate that mutations within the Grb2 consensus sequence do not affect
RNA synthesis (conventional RT-PCR) or protein synthesis (western blot
analysis). Through the application of
fluorescent confocal microscopy and western blot analysis of isolated cell
membranes, we have shown that these mutations do not alter localisation of
NET to the membrane. Samara
Finch and David Kaye are currently examining the role of atrial fibrillation in heart
failure. Previous research has shown that baroreceptors are blunted in CHF
and that this is associated with prognosis. Previously, we have shown that
sympathetic activity is not further elevated with atrial fibrillation in CHF
at rest in a well treated group of patients, but the affect atrial
fibrillation has on baroreceptor response in CHF and on sympathetic response
to exercise is unknown. Our studies have shown that AF further impairs
sympathetic response to baroreceptor unloading in CHF and postulated that the
mechanism is secondary to atrial fibrosis. Subsequent to this, we collected
right atrial appendages from cardiac surgical patients (11 in atrial
fibrillation and 11 in sinus rhythm) and have shown significant increases in
collagen content in atrial fibrillation patients by Sirius red staining. To
further extend the research into the haemodynamic impairment and outcome of
heart failure patients with atrial fibrillation a Real Time RT-PCR method was
developed to examine the mRNA expression profile of Nerve Growth Factor (NGF)
in atrial fibrillation and SR. NGF is essential for the development and maintenance
of sympathetic neurons. Recent Publications
1. Parnell MM, Holst DP, Kaye DM.
Augmentation of endothelial function following exercise training is
associated with increased L-arginine transport in human heart failure. Clin
Sci (Lond). 2005;109:523-30. 2. Gould PA, Yii M, Esler MD, Power JM, Kaye
DM. Atrial fibrillation impairs cardiac sympathetic response to baroreceptor
unloading in congestive heart failure. Eur Heart J. 2005;26:2562-7. 3. Kiriazis
H, Du XJ, Feng X, Hotchkin E, Marshall T, Finch S, Gao XM, Lambert G, Choate
JK, Kaye DM. Preserved left ventricular structure and function in mice with
cardiac sympathetic hyperinnervation. Am J Physiol Heart Circ Physiol.
2005;289:H1359-65. 4. Kaye D, Esler M. Sympathetic neuronal
regulation of the heart in aging and heart failure. Cardiovasc Res.
2005;66:256-64. 5. Kaye DM, Smirk B, Finch S, Williams C,
Esler MD. Interaction between cardiac sympathetic drive and heart rate in
heart failure: modulation by adrenergic receptor genotype. J Am Coll
Cardiol. 2004;44:2008-15. |
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Molecular Pharmacology: Dr Rebecca Ritchie
Abnormalities in myocardial function, particularly diastolic
dysfunction, and the cardiac hypertrophy and fibrosis (see Figure) that can
underlie these functional problems, are characteristic of the diabetic heart,
and likely contribute to the high incidence of cardiovascular mortality in
diabetic Australians.
We have evidence that increased steady-state levels
of reactive oxygen species, from NADPH oxidase and other sources
(mitochondria, uncoupled nitric oxide synthase, NOS), is a contributing
mechanism to these diabetic cardiac complications in vivo. Thus, our ongoing
studies across cardiomyocyte hypertrophy, ischaemia-reperfusion, and the
diabetic heart suggest that administration of effective reactive oxygen species-limiting
therapies, alone or on top of current therapy, will likely have incremental
cardiac benefit in affected patients, limiting progression to heart failure
and mortality. |
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Recent Publications |
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1. |
Rosenkranz AC, Hood SG, Woods RL,
Dusting GJ, Ritchie RH. (2003). B-type natriuretic peptide prevents acute
hypertrophic responses in the diabetic rat heart: importance of cyclic GMP.
Diabetes 52: 2389-2395. |
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2. |
Ritchie RH, Rosenkranz AC, Huynh LP, Stephenson T,
Kaye DM, Dusting GJ (2004). Activation of IP-prostanoid receptors prevents
cardiomyocyte hypertrophy via cyclic AMP-dependent signaling. Am J Physiol
287: H1179-H1185. |
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3. |
Ritchie RH, Gordon JG, Cao AH, Woodman OL, Dusting
GJ. (2005). Annexin-1 peptide Anx-12-26 protects adult rat cardiac myocytes
from cellular injury induced by simulated ischaemia. Br J Pharmacol 145(4):
495-502. |
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4. |
Ritchie
RH, Delbridge LM. (2006) Cardiac hypertrophy, substrate utilisation and
metabolic remodelling -cause or effect? Clin Exp Pharmacol Physiol 33:
171-178. |
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5. |
Garreffa
AM, Woodman OL, Cao AH, Ritchie RH. (2005). Sodium nitroprusside protects
adult rat cardiac myocytes from cellular injury induced by simulated
ischemia: role for a non-cyclic GMP-dependent mechanism of nitric oxide
protection. J Cardiovasc Pharmacol 47(1): 1-8. |
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Centre
for Thrombosis & Myocardial Infarction: Professor Karlheinz Peter
Anti-platelet therapy and
anticoagulation are the cornerstones of the acute treatment as well as the
prevention of myocardial infarction. However, limited efficiency and adverse
effects, in particular bleeding complications, have prompted intensive search
for better therapeutic agents. Professor
Karlheinz Peter heads a
newly created Centre for Thrombosis &
Myocardial Infarction at the
Baker Heart Research Institute in Melbourne. The Centre spans from basic research
in molecular biology to clinical trails in cardiology. This includes studies
on the cellular mechanisms of coronary artery disease, encompassing the role
of platelets, coagulation and inflammation in atherosclerosis, as well as the
mechanisms leading to the rupture of atherosclerotic plaques. One of
Karlheinz’s major goals is the development of so-called “intelligent” drugs,
tailored to specifically block only activated platelets in the circulating
blood, or to provide anticoagulation only at the clot, the site where it is
needed most. This approach is based on single-chain antibodies that were
generated from human single-chain antibody phage libraries. These recombinant
antibody fragments are directed against epitopes, which are only present on the
activated GPIIb/IIIa receptor and are thus specific for activated platelets.
Thereby, the treatment and/or prevention of myocardial infarction and stroke
should be more efficient and the risk of bleeding complications should be
reduced markedly. The first promising agents have already been developed
within the Centre. |
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Centre for Thrombosis & Myocardial Infarction left to right, Dexing Huang, Yung Chih Chen, Ruide Koh, Vicki
Wong, Dr. Christoph Hagemeyer, Dr. Madhara Udawela, Dr. Steffen Eisenhardt,
Prof. Karlheinz Peter, Dr. Juliana Soosairajah |
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Karlheinz obtained his MD and PhD at the University of
Freiburg, Germany, where he also spent several years in clinical practice as
a cardiologist, most recently as the head of the cardiac catheter laboratory.
He worked as post doctoral research officer at the Johns Hopkins University,
Baltimore, USA and at the Scripps Research Foundation, San Diego, USA. Most
of his clinical training was done at the University of Heidelberg, Germany.
Karlheinz was attracted to the Baker Institute by its unique combination of
clinical and basic research, made possible by the partnership with The Alfred
Hospital, Monash University, and the Australian Centre for Blood Diseases. |
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Recent Publications |
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1. |
Ahrens I, Moran N, Aylward K, Meade G,
Moser M, Assefa D, Fitzgerald DJ, Bode C, Peter
K. Evidence for a differential functional regulation of the two beta(3)-integrins alpha(V)beta(3) and
alpha(IIb)beta(3).Exp Cell Res. 2006 Jan 20; [Epub ahead of print] |
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2. |
Schwarz M, Röttgen P, Takada Y, Le Gall
F, Knackmuss S, Bassler N, Büttner C, Little M, Bode C. Peter K. Single-chain
antibodies for the conformation-specific blockade of activated platelet
integrin aIIbb3 designed by subtractive selection from naïve human phage
libraries. FASEB J 2004;18:1704-06.
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3. |
Kanse SM, Matz-Westphal R,
Preissner KT, Peter K. Vitronectin is a ligand for the b2 integrin Mac-1
(aMb2, CD11b/CD18) and this interaction promotes leukocyte adhesion. Arteriosclerosis,
Thrombosis and Vascular Biology 2004;24:2251-6 |
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4. |
Hagemeyer C, Tomic I, Weirich U,
Graeber J, Nordt T, Runge MS, Bode C, Peter K. Construction and
characterization of a recombinant plasminogen activator com-posed of an
anti-fibrin single-chain antibody and low molecular weight urokinase. J.
Thrombosis and Haemostasis 2004;2:597-803. |
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5. |
Hagemeyer C, Tomic I, Jaminet P, Weirich U, Bassler
N, Schwarz M, Runge MS, Bode C, Peter K. Fibrin-targeted direct factor Xa inhibition:
Construction and characterization of a recombinant factor Xa inhibitor
composed of an anti-fibrin single-chain antibody and tick anticoagulant peptide. Thrombosis and Haemostasis
2004;92:47-53. |
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Molecular
Endocrinology Laboratory: Dr Walter Thomas
Our aim is to understand the processes that allow membrane receptors to
transmit signals and affect cell function, including the mechanisms used by
cells to limit signalling and permit responses of appropriate strength and
duration. Specifically, our research
focuses on seven transmembrane spanning, G protein-coupled receptors (GPCRs)
that represent the largest receptor superfamily in our genome. Mutations
and modifications of GPCRs and their signalling and regulatory partners are
linked to dysfunction and disease and drugs that target these receptors are
prime candidates for therapy. We
study the activation and deactivation of two main,
clinically relevant GPCRs – the angiotensin type 1 receptor and urotensin II receptor. Perturbations in these systems are linked
to hypertension and cardiovascular disease and significant insights into the
biology of receptor systems have already impacted clinical practice (eg, the
use of non-peptide AT1 receptor antagonists to alleviate high blood pressure
and reduce mortality). Our research
group consists of post-doctoral fellows, research and technical assistants,
and PhD and honours students (see photo) and funded collaborations with Ross
Hannan, Mibel Aguilar, Andrew Allen, and Stephen Harrap (et al.). |
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Molecular Endocrinology Laboratory, Back row: Angelo D’Amore, Nicola Smith, Cristina Oro, Walter
Thomas, Hongwei Qian, Front row: Luisa Piplol, Thao Pham, Diem Dinh, Hsiu-wen
Chan, Japreet Dosanjh, Enzo Porello, Inset: Gabrielle Callander, John Huynh,
Allison Bourne, Absent: Len Pattenden, Erin O’Callaghan, Ann Du |
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Our research efforts are aligned to the four NHMRC
project grants currently held, particularly my two CIA NHMRC projects. One is a 5-year project grant based on our
discovery that angiotensin receptor activation induces cardiac cell growth
and signalling via trans-activation of the epidermal growth factor
receptor. Our research dissects and
understands EGFR trans-activation from a molecular, cellular and in vivo
perspective. Outcomes will provide
important information on, and potential targets for, left ventricular
hypertrophy – a major independent risk factor for cardiac failure and
death. The other 3-year project grant
focuses on the molecular and cellular processes that dictate activation and
trafficking of regulatory and scaffolding proteins termed arrestins, as well
as the contribution of arrestins to the complexity of GPCR function. Outcomes
from these studies will offer new possibilities for blocking/augmenting GPCR
actions – particularly, angiotensin and urotensin receptors that contribute
significantly to human health and disease.
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Neuropharmacology
Laboratory: Associate Professor Geoffrey Head
Increased activity of the sympathetic nervous system (SNS) occurs in
both hypertension
and congestive heart failure. The focus of the Neuropharmacology Laboratory,
led by Geoff
Head,
(NHMRC Principal Research Fellow), is to understand how brain pathways and
neurotransmitters regulate the cardiovascular system and to discover the
mechanisms responsible for the overactivity of the SNS in these diseases. An
understanding of this process may reveal how the SNS may contribute to the
long term regulation of blood pressure. Role
of the SNS in Angiotensin Dependent Hypertension
We have found that centrally
acting antihypertensive drugs that inhibit the SNS are much more effective in
normalising blood pressure in this form of hypertension, suggesting an
overactive SNS. This is supported by our recent evidence that ganglionic
blockade produces a much greater fall in blood pressure in hypertensive
animals. However, directly recorded renal sympathetic nerve activity is not
elevated when the hypertension is established. This may be explained by a
greater neuroeffector response, an altered pattern of sympathetic activity or
possibly a contribution from vascular remodeling. Sandra Burke
and MSc
student John-Luis
Moretti
are determining the importance of the renal
nerves and the role of vascular hypertrophy, in the development of
angiotensin dependent hypertension. Geoff and Sandra have been collaborating
with Roger
Evans
from Monash University and Gavin Lambert, to investigate whether this
paradox may be explained by an increased neuroeffector mechanism in the
kidney. Pamela
Davern,
recently arrived from the Howard Florey Institute and currently completing
her PhD, has used immunohistochemical methods with Fos related antigen (FRA),
to investigate brain regions responding to long term activation by
angiotensin and to identify nuclei that may be relevant to sympathetic nerve
activation. |
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Neuropharmacology Laboratory from left to right: James
Armmitage, Lihonh Kong, Pamela Davern, Daian Chen, Geoff Head, Genevieve
Martin, Dmitry Mayorov, Thu-Phuc Nguyen-Huu, Sandra Burke and Luisa La Greca |
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Central
Cardiovascular Pathways involved in stress and L-NAME induced hypertension
Having established a role for
central angiotensin and its subsequent activation of hypothalamic and
brainstem superoxide cell signalling during stress, Dmitry Mayorov, HBPRCA Fellow, Honours
student Daian Chen, and Geoff Head are now working to determine the sources of
superoxide production, the downstream products and the signalling pathways.
They also plan to explore how these systems contribute to the long term
adaptive changes that occur with chronic emotional stress using AT1
receptor knockout mice. There is evidence that increased activity of NADPH
oxidase at the level of pre-sympathetic nuclei of the hypothalamus and
brainstem contributes to the maintenance of L-NAME-induced hypertension. James Armitage, recently arrived after
3 years in London as a Postdoctoral Research Fellow, Maternal and Fetal
Research Unit at King’s College, is examining the effect of chronic treatment
with L-NAME on BP in order to assess the contribution of the SNS to the
hypertension. They will now determine the expression of gp91phox and p47phox
subunits of NADPH oxidase in the hypothalamus and rostroventrolateral
medulla. Cardiovascular
effects of Taipan natriuretic peptides
Natriuretic peptides which act in
the body to oppose the activity of the renin-angiotensin system and enhance
excretion of sodium and water, are found in many species. In collaboration
with Professor
Alewood
at the Institute for Molecular Bioscience University of Queensland we have
examined a series of peptides isolated from the venom of the Taipan which
have activity similar to the human natriuretic peptides. Geoff Head and Lihong Kong, who recently completed
her PhD at University of NSW, have been characterizing the
cardiovascular actions of these peptides and a number of newly synthetized
analogues in conscious rabbits and in heart failure rats. This project has
become a commercial development with the formation of a new spin-off company Elacor. Cardiovascular
Profile Of Aromatase (Estrogen Deficient) Mice
There has
been much interest in the cardiovascular role of estrogens with the
consistent findings that men and postmenopausal women are at higher risk of
developing cardiovascular disease than premenopausal women. We now have
access to mice lacking estrogen because the enzyme aromatase has been knocked
out and have shown they have lower blood pressure and baroreflex sensitivity.
In a collaboration with Margaret Jones at
Monash University, Honours student Thu-Phuc Nguyen-Huu will examine the effect of a high salt diet and estrogen replacement
on these mice using radiotelemetry to measure blood pressure, as estrogen may
be protective against the adverse effects of a high salt diet. Morning Surge In Blood Pressure as a Risk Factor In
Cardiovascular Disease
It is well recognised that the
occurrence of strokes and cardiac infarcts in humans is highest in the
morning when blood pressure is rising from low overnight values. Geoff and Elena Lukoshkova, a scientist from Moscow, have developed a logistic
curve fitting procedure which measures the diurnal rates of transition in
cardiovascular variables and from the active to the asleep periods
separately. As part of a larger collaborative effort with Barry McGrath (Dandenong Hospital) and Chris Reid, Melinda Carrington, (PhD
pending), and Honours Student Nicola Fotheringham are characterising
predictors of the rate of morning rise in blood pressure and heart rate in a
large patient group to determine whether subjects with an excessive morning
surge have altered functioning of the SNS and whether there is a relationship
with vascular compliance. Aetiology of Obesity Related Hypertension
Up to 70% of newly diagnosed hypertension in
the Framingham study is attributed to obesity, and study of obesity and its
related cardiovascular risk is an emerging focus. Geoff and Nina Eikelis have
shown that obese rabbits are resistant to the central effects of leptin in
relation to satiety but not with regard to SNS activation. This suggests that
leptin resistance at the level of the hypothalamus is selective to appetite
regulation and that continued stimulation of SNS vasomotor tone may drive the
hypertension observed with obesity. James, Geoff, Luisa LaGreca and Genevieve Martin (RMIT Pharmaceutical Science student) are
examining the neurogenic mechanisms underpinning the development of obesity
related hypertension in rabbits by characterising changes in CNS pathways
that modulate SNS activation (by FRA immunohistochemistry and targeted
blockade of hypothalamic nuclei) early during the consumption of a high fat
diet. We believe that changes in sympathetic vasomotor tone may occur very
early during the development of obesity and that the selective CNS changes
that result in this neurogenic form of hypertension may be pivotal in the
development of obesity related cardiovascular disease. Recent Publications |
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1.
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Head GA, Mayorov DN. Imidazoline
receptors, novel agents and therapeutic potential. Cardiovascular & Hematological
Agents in Medicinal Chemistry. 2006;4:17-32.
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2.
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De Matteo R, Head GA, Mayorov DN.
Angiotensin II in dorsomedial hypothalamus modulates cardiovascular arousal
caused by stress but not feeding in rabbits. Am J Physiol Regul Integr Comp
Physiol. 2006;290:R257-R264.
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3.
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Mayorov DN. Selective
sensitization by nitric oxide of sympathetic baroreflex in rostral
ventrolateral medulla of conscious rabbits. Hypertension. 2005;45:901-906.
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4.
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Head GA, Lukoshkova E, Reid CM.
Non-symmetrical double logistic analysis of ambulatory blood pressure
recordings. J Appl Physiol. 2005;98:1511 1518.
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5.
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Chan CK, Burke SL, Zhu H, Piletz JE,
Head GA. Imidazoline receptors associated with noradrenergic terminals in the
rostral ventrolateral medulla mediate the hypotensive responses of moxonidine
but not clonidine. Neuroscience. 2005;132:991-1007.
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Athina Patti at Meetings First t 61 3
9739 7697 f 61 3
9739 7076 |
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CORPORATE MEMBERS HBPRCA would like to acknowledge the ongoing support of
the following corporate members:
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MEETINGS
IN 2006 |
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Experimental Biology 2006
1 - 5 April 2006 Moscone Convention centre,
San Francisco, CA, USA Click here for the meeting website
Click here for the society website |
American Society of Hypertension
Annual meeting
May 17 - 20, 2006 New York City, Hilton Hotel Click here for the meeting
website Click here for the society website |
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European Society of Cardiology Heart Failure 2006 17 - 20 June 2006
Helsinki, Finland
Click here for the meeting website
Click here for the society website |
World Congress of Cardiology 2006
“Bringing together the European Society of Cardiology
Congress 2006 and the World Heart Federation's XVth World Congress of
Cardiology” 2 - 6 September 2006
Barcelona, Spain
Click here for the meeting website
Click here for the society website |
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International Conference on Healthy
Ageing and Longevity
3rd Annual Meeting
Friday, October
13 – Sunday, October 15, 2006 Melbourne,
Australia Click here for meeting website
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International Society of
Hypertension
21st Scientific Meeting15 - 19 October
2006 Fukuoka, Japan Click here for meeting website Click here for International Society of hypertension web page |
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