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High Blood Pressure Research Council of Australia |
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HBPRCA
Email Newsletter
March
2007
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Welcome to the first
e-news of the year. In this issue Stephen gives an update of the “Better
Blood Pressure Measurement” initiative, Jaye outlines the exciting plans
for the 2007 ASM in Adelaide in December and Paul Korner provides a
glimpse of his new, soon to be released book “Essential Hypertension and Its Causes: Neural and Non-Neural
Mechanisms” as the major feature article for the issue. With best wishes, Geoff Head |
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PRESIDENT’S MESSAGE from Stephen Harrap As you are all aware, the Better
Blood Pressure Measurement Initiative launch was held at the Royal Australian
College of General Practitioners Annual Meeting in October 2006. The
Council and Executive have busy over the recent months preparing for the
roll-out of Omron semi-automated digital blood pressure machines as part of
this initiative. The first monitor was delivered on 23 January 2007,
and this stage we have delivered almost 10,000 machines and we have
already received good feedback from GPs. The plan is to have all blood
pressure machines delivered to GP’s across Australia by World Hypertension
Day, 17 May 2007. So far we have received considerable positive
publicity. Please click here
to view a media summary, which includes press articles, radio interviews,
television appearances and website publications, that were held during the
launch. Channel nine also broadcasted an interview. To view this video clip,
please click here. At the same time Mark Nelson and
his team in Tasmania have commenced the Cluster Randomised
controlled trial of an Automated versus manual device for Blood
pressure management (CRAB) Study, which is part of the research arm of the
initiative. CRAB will evaluate just how the availability of these machines
might change BP measurement practices in GP clinics. This research is being
supported by the Council as part of the initiative and we are also planning
to support other research along similar lines.
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MEETING NEWS from Jaye Chin Dusting Plans are well underway for the 2007 HBPRCA Annual
Scientific Meeting to be held in Adelaide 5-7 December this year. This will
be a joint HBPRCA-ASCEPT-SEAWP meeting and thus a wide audience particularly
in the joint sessions are anticipated.
The joint sessions will start from Wednesday 5 December and include
the Austin Doyle Lecture and two focus sessions. Our 2007 Austin Doyle Lecturer is Ian Frazer, from the
University of Queensland, who of course, received the 2006 Australian of the
year award on his ground-breaking work in papilloma virus and cervical
cancer. The joint focus sessions are
"Cardiovascular Genetics" and "Oxidative Stress", which
will feature invited talks as well as selected free communications from
abstract submissions. We received some fantastic suggestions for the RD Wright
and Colin Johnston Lectureships again this year; frankly I am having such a
difficult time ranking them in order of priority - I have put it in the too
hard basket for the moment! I guess
you will just have to trust that any one of the nominated suggestions
received will be worthy recipients of the honour and will contribute well to
a meeting already shaping up to be a "not to be missed". Mark it in your diaries. |
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MEMBERSHIP
NEWS 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 (www.hbprca.com.au)
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 (free
for students!). The special initiatives that have been introduced are
specifically intended to benefit student and early career members. And of
course participating in the vibrant Annual Scientific Meeting is a tremendous
opportunity for you, your post-docs, students and research associates to see
and discuss the broad research interests of the council and share your own. |
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INTER-SOCIETY
LIAISON from
Kate Denton HBPRCA Young
Investigator Award 2006 Dr James
Sharman, Department of Medicine, Princess Alexandra Hospital, Queensland The British Hypertension
Society has been informed and is preparing to make welcome our Young
Investigator Award winner Dr James Sharman, whose presentation was "
Patients with type 2 diabetes mellitus have an exaggerated brachial and
central blood pressure response to exercise: relation to left ventricular
hypertrophy", James is from Tom Marwick's group at the Department of
Medicine, Princess Alexandra Hospital, Queensland. British
Hypertension Society Annual Meeting, which is on 24-26th September 2007 at St
John's College, Cambridge. James' talk will be scheduled prior to the
Pickering Lecture at 12noon on 25th September. The winners of this award are certainly well looked after
during their visit! American Council for High Blood Pressure Research Unfortunately,
the only company that did not restrict the travel awards has pulled out of
CHBPR this year. Thus, it appears that there may not be any travel funds
available to support young investigators from Australia, despite excellent
progress in this regard last year. What other groups from overseas
have done is to contact the drug companies in their own countries and
convince them to set up a travel award fund to support their own young
investigators. The HBPRCA is looking
into this option. Foundation
for High Blood Pressure Research (FHBPR) I would remind everyone that the FHBPR offers travel
grants to our membership. These are
available for attendance at national or international meetings with a
cardiovascular theme. There is no
formal application procedure. To apply the applicant should write to the
secretariat of the FHBPR stating briefly what your current position is, the
details of the meeting you will be attending and what your role will be
(invited speaker, abstract submitted etc). A fixed amount is given for a
national or international meeting if the applicant is approved by the
foundation. FHBPR Secretariat Department of Physiology University of Melbourne Parkville VIC 3010 Australia Email: jkelly@umimelb.edu.au
British Hypertension Society Young Investigator Award
2006 Emma Mead, Clinical Pharmacology Unit, University of
Cambridge Report from the HBPRCA 2006 meeting - Brisbane
This provided me with an
exciting opportunity to present my work to an entirely new audience and gain
some interesting new perspectives and insights into my findings. I was made
to feel very welcome by the society and would particularly like to thank
Athina Patti and Kate Denton for all their help in organising the trip and
Michael Stowasser for coming to meet me from the airport. The meeting was excellent with a
broad range of clinical and basic science. A highlight for me was the
organisation of the poster prize sessions. It was wonderful to see how by
presenting these via the projector so many people were able to be involved in
the discussion of the work with the presenters. I also particularly noted the
great enthusiasm in the society, which was reflected in the high quality of
all of the young investigators. It was a pleasure to see Enzo Porrello again after he set such high
standards at the 2006 British Hypertension Society meeting. I look forward to
welcoming the winner of this years Early Career Award James Sharman to
Cambridge in 2007, congratulations to him on a fantastic presentation and I
hope we can make him feel as welcome as the HBPRCA made me. While in Brisbane I was also
fortunate to visit the laboratory of Peter Molenaar, an expert in beta
adrenoreceptors, in the department of Malcolm West. This was an interesting
visit not only because Peter Molenaar had previously worked in the Clinical
Pharmacology Unit, Cambridge, but also it gave me fresh ideas for future
work. All that remains is for me to express my sincere thanks to Stephen
Harrap and Morris Brown for continuing this intuitive between the two
societies and providing young investigators, such as myself, with the chance
to present their work to an international audience and to my supervisor
Anthony Davenport who has supported me throughout my PhD. |
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FEATURE ARTICLE – PAUL KORNER Essential Hypertension and Its Causes: Neural and Non-Neural
Mechanisms, by Paul Korner. Oxford University Press, New
York, 2007. 716 pp, 325 figs, 72
tables The word "essential"
in essential hypertension (EH) means high blood pressure (BP) of unknown
cause, and this is how EH is still widely regarded. This may be due to the
multifactorial nature of EH and to uncertainty about the role of the
kidney. Some 40 years ago Arthur
Guyton suggested that every type of high BP began as volume overload arising
from an inability of a dysfunctional kidney to excrete salt. This certainly
does not apply to EH in which blood volume is low and the kidney is the
victim rather than the source of the high BP. Guyton thought the autonomic
nervous system played no role in long-term regulation of BP, but we now know
that sympathetic neural activity (SNA) is raised in EH. Clearly, a fresh synthesis of the vast
amount of available information on EH has long been overdue. This became clear when examining
the nature of the circulatory control system itself. Most cardiovascular physiologists still
regard this as a linear feedback system with fixed parameters and set
point. However, it resembles in fact
a non-linear man-made "adaptive" control system, in which
parameters are actively altered when the operating conditions exceed certain
limits. Such parameter changes can occur either acutely, as in haemorrhage
during transition from the non-hypotensive to the hypotensive phase, or
chronically, as in regular exercise training or in chronic mental stress. BP Genetics We now know from many biometrical studies that genes
and environment are both crucial in the development of EH. In contrast, in
the Japanese spontaneously hypertensive rat (SHR) the genetic influence is
stronger and hypertension develops in almost every environment. The borderline hypertensive rat (BHR, i.e.
the F1 hybrid of SHR×WKY), with half the high BP genes of SHR,
provides a better animal model that simulates what happens in EH: their blood pressure (BP) only rises in
the presence of environmental reinforcement by chronic stress or a high salt
intake. Unfortunately to date none of the high BP genes have
been definitively identified in either EH or SHR. However we know at least
that there is a strong probability that some trait differences are
genetically determined. Human subjects with a family history of EH respond
more strongly to stress tests than those without such a history. In inbred
animals there is a strong likelihood for a genetic basis for a trait
difference between, for example, SHR and normotensive WKY, if it cosegregates
with BP in F2 or backcross populations. This has been demonstrated
for resting SNA, for SNA responses to acute stress and for several other traits. It suggests that failure to
identify the underlying genes in EH and animal models of neurally initiated
hypertension may be due to neglect of the brain by those working on the
field. Environmental
Causes and Output Patterns as EH Becomes More Severe We know from various case control
and intervention studies, that the main environmental causes initiating EH
are mental stress, a high salt intake and obesity. The early rise in BP is
largely due to elevation of SNA in the outflows to the heart, renal,
gastrointestinal, skin and skeletal muscle beds, with the secretion of
adrenaline tending to mask the skeletal muscle vasoconstriction. This is the
defence pattern of autonomic activity, which arises from specific
hypothalamic neuron groups. Non-neural enhancement of vasoconstrictor tone is
initially through cortisol-induced reduction in regional nitric oxide (NO),
which accentuates the effects of the raised SNA. Later structural changes
develop in the large resistance vessels and enhance the overall functional
constrictor effects, raising BP further. The vasoconstriction also results in
deterioration of the downstream microcirculation, which is known as
rarefaction. Eventually the function of kidney, brain and heart become
impaired. The above peripheral changes and
the stiffening of the conduit arteries make substantial demands on the
heart's pump performance. This is provided by increased inotropic support,
development of left ventricular hypertrophy and an adequate coronary blood
flow. Eventually an inability to match the peripheral changes produces
cardiac failure. Brain Mechanisms All major autonomic effector
responses are mediated through neurons that release fast (rapidly acting)
transmitters, e.g. glutamate. Other
interneurons that carry information from one neuron population to another,
release slow transmitters, including monoamines and various peptides. Each slow transmitter modulates the
responsiveness of the fast transmitter pathways. For example, in EH (and
SHR), repeated increase in dopamine (DA) neuron activity strengthens synaptic
transmission of the hypothalamic defence pathway and lowers the threshold for
eliciting the sympatho-adrenal changes, which is termed sensitization and is
a relatively irreversible process. Baroreflexes contribute to
virtually all aspects of circulatory control. In the intact organism the
responses depend on the combined changes in arterial, cardiac and pulmonary
baroreceptor activity. In every type of hypertension there is a chronic
increase in cardiopulmonary load, which gives rise to the well-known vagal
deficit, which is evoked through serotonergic neurons stimulated by an
increase in activity from medium-high threshold baroreceptors. The vagal deficit disappears rapidly when
volume load is reduced. Exercise is a physiological
variant of the defence response and is associated with elevation of BP and
enhancement of constrictor baroreflexes. Its regulatory drive arises from
cortical "command" neurons and from muscle chemoreceptors, both of
which interact with the baroreflex pathways. The cerebellum compares actual
to desired skeletal muscle performance and adjusts both muscle performance
and SNA in the light of this comparison.
It may also be responsible for the transient depression of constrictor
baroreflex properties between regular training sessions, that is one factor
mediating the anti-hypertensive effect of exercise. The Main Syndromes
of EH There are two syndromes: 1)
stress-and-salt related EH (SSR-EH), and 2) hypertensive obesity. Both are
initiated by psychosocial stress, with the hypothalamic defence response the
basis for the initial elevation of BP. Stress is perceived through the
thalamo-cortical system and its intensity is evaluated by the prefrontal
cortex. Activity of DA neurons that link the latter to the hypothalamus is
responsible for the chronic elevation of BP and sympatho-adrenal activity. In
normal subjects these changes revert to baseline when the stress is over.
However, in persons genetically susceptible to EH, sensitization of defence
pathway synapses leads to virtually permanent elevation of BP, outlasting the
stress. Synaptic sensitization is a
normal attribute of thalamocortical and memory neurons, but is most unusual
in the autonomic nervous system. It suggests that in persons susceptible to
EH mutant developmental genes may give rise to ectopic DA synapses with their
properties resembling memory neurons.
The chronic vasoconstriction
that follows sensitization of the defence pathway increases BP responsiveness
to salt by raising sodium permeability of the blood-brain barrier. This
increases the activity of brain ouabain neurons that raise BP and SNA through
projections to the defence area. Salt
thus adds to the stress-related neural increase in BP, resulting in a
combined initial rise in BP of about 20 mm Hg. Nonneural factors account for
the subsequent further rise of 20-40 mm Hg. There is considerable individual
variation in the magnitude of this latter rise, which may also have a genetic
basis.
Prevention and
Treatment Remarkably, the major benefit of
most anti-hypertensive drugs is largely through non-specific lowering of BP.
This reduces myogenic tone and widens the diameter of the resistance vessels.
The cardiovascular structural changes associated with EH are difficult to
reverse, though some drugs appear to bring this about more than others,
particularly in younger persons. In contrast to the largely non-specific
effects of the drugs, the major non-pharmacological forms of management
(exercise and reduction of dietary intake of salt and calories) are
relatively specific antagonists of the initial SNA-induced elevation of
BP. Hence, if they became part of a
persons lifestyle from an early age, EHmight be prevented. In established EH,
these measures should be used more energetically than at present in
conjunction with pharmacotherapy, particularly in the treatment of young and
middle aged persons with EH. In at least a proportion of this group it may
become possible to wean them off anti-hypertensive drugs. Other Topics Obesity also predisposes to
obstructive sleep apnea (OSA), which results in elevation of BP. Some regard
OSA as another syndrome of EH, but most consider it to be a secondary form of
high BP, which develops as a consequence of the nasopharyngeal obstruction.
Other factors contributing to EH, including smoking, alcohol intake and other
dietary factors have also been considered briefly. There is a chapter on the role
of the kidney in hypertension. It discusses the interpretation of renal
transplantation experiments, which have figured extensively in theories
regarding the kidney as the source of hypertension. Renal involvement in EH
is more gradual than in renal hypertension, in which SNA is also elevated
when there is renal ischaemia. Lastly, a chapter on the
pathogenesis of SHR hypertension emphasises the critical role of elevation in
SNA in the development of the high BP. Conclusion The brain is the source of the
initial rise in BP, through a variant response to the world around us. The
present synthesis suggests that it may be timely to refer to EH from now as
lifestyle-related genetic hypertension.
There is a strong case for employing physiological systems analysis
when trying to elucidate the pathogenesis of complex disorders like EH. This will help elucidate how critical
system components operate at the molecular level, which will eventually lead
to new forms of therapy. |
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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 sponsors:
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MEETINGS IN
2007 |
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Society
for Endocrinology BES 2007 5 – 8
May 2007 Birmingham Click here for
meeting website |
8th International Conference of Nuclear Cardiology
- ICNC8 29 April – 2 May 2007 Prague - Czech Republic Click here for
meeting website |
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7th BHS Clinical Education Meeting for Primary Care 20 April 2007 Royal College of Physicians, London Click here for
meeting announcement |
XVIIth Scientific Sessions of the Inter-American
Society of Hypertension (IASH) 6 – 10 May 2007 Miami Beach, Florida, USA Click here for
meeting website |
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Lipids in Clinical Medicine Section: Obesity and
adipose tissue biology 10 May 2007 Click here for meeting website |
American
Society of Hypertension 19 – 23 May 2007
Chicago
Click here for
meeting website |
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Lindon Wing Festschrift 24 – 15 May 2007 Adelaide, Australia Click here for more information. |
Metabolic Syndrome: fatty livers and arteries Royal College of Physicians, London Click here for meeting website |
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Heart Failure 2007 9– 12 June 2007 Hamburg - Germany Click here for
meeting website |
17th European Meeting on
Hypertension 15 – 19 June 2007 Milan Click here for meeting website |
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Europace 2007
24 – 27 June 2007 Lisbon – Portugal Click here for
meeting website |
H.E.A.R.T UK 21st Annual Medical & Scientific
Meeting 27 – 29 June 2007 Edinburgh Click here
for
meeting website |
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Key Advances in the Management of Hypertension
(joint RSM/BHS Meeting) 4 July 2007 Click here for meeting website |
ESC Congress 2007 1 – 5 September 2007 Vienna – Austria Click here for
meeting website |
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Annual Scientific Meeting of the British
Hypertension Society Click here for meeting website |
61st High
Blood Pressure Research Conference 2007 26 – 29 September 2007 Tucson, AZ, USA Click here for
meeting website |
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2007 Cardiometabolic Health Congress 27 – 29 September 2007 Boston, MA, USA Click here for meeting website |
High Blood Pressure Research Council of Australia’s
Annual Scientific Meeting 5 – 7 December 2007 Adelaide, South Australia Click here for
meeting website |
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MEETINGS IN
2008 |
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2nd International Conference on Hypertension,
Lipids, Diabetes and Stroke Prevention 6 – 8 March 2008 Prague, Czech Republic Click here for meeting website |
ISH 2008 – The 22nd Scientific Meeting of the
International Society of Hypertension 14 – 19 June 2007 Click here for meeting website |
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Annual Scientific Meeting of the British
Hypertension Society Click here for meeting website |
2nd International Symposium on Pheochromocytoma 17 – 20 September 2007 Click here for meeting website |
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