High Blood Pressure Research Council of Australia



HBPRCA Email Newsletter

March 2007


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



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.

Plans are also underway for creating a new and improved website on which we shall place educational information for GPs about recent research on BP. This is part of the educational arm of the Better Blood Pressure Measurement initiative, allowing us to employ web designers and medical writers. This will be overseen by Bruce Neal from the George Institute who has kindly agreed to act as Editor of the research bulletins for GPs (they will also be sent directly by email to GPs where possible) and we shall be hoping to draw upon the experts in the Council to write or check very brief commentaries on the research and it relevance to GPs.

We have been working on 2 initiatives, one supported by an Educational Grant from sanofi-aventis, the other supported by Bristol Myers Squibb. These 2 initiatives dovetail beautifully together and with the Better Blood Pressure Measurement initiative. One will campaign for more widespread understanding of BP along the lines of “knowing your own BP”. The other will provide GPs with information about measuring BP – techniques, pitfalls, special circumstances, machine calibration, etc.

The Council is also involved with a BP awareness campaign with the National Stroke Foundation and I am grateful to Lindon Wing and Karen Duggan, who will be representing the Council on the Expert Advisory Committee.

So 2007 will a busy year for the Council and its public profile and impact. Looking to December, don’t forget to put the Annual Scientific Meeting in your diaries for Dec 5 to 7 in Adelaide. There is more news about this meeting from Jaye next in this eNews. Suffice to say that it will be a terrific meeting.



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.



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.




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


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

As the winner of the 2006 British Hypertension Society Young Investigators Award I was extremely honoured to attend the Annual Scientific Meeting of the High Blood Pressure Research Council of Australia in 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.




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.

Hypertensive obesity is the second syndrome of EH: it is due to superposition of obesity on SSR-EH and accounts for about 40% of all EH.  It is a volume overload hypertension, in which the stress-related vasoconstriction is masked by the dilator action of the raised plasma insulin. Insulin also increases fluid reabsorption by the renal tubules. In lean persons with EH the brain mechanisms regulating energy balance function normally in response to changing levels of leptin and other adiposity peptides.  However, in a proportion of persons with the cortex ignores these signals: their excess eating is a response to alleviate stress-related anxiety and leads to obesity. Unfortunately, the effect is only transient and their eating eventually becomes an addiction. Subjects with hypertensive obesity develop distinctive complications, notably non-insulin dependent diabetes mellitus and LV failure.


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.



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.





HBPRCA Secretariat

Athina Patti at

Meetings First

t          61 3 9739 7697

f          61 3 9739 7076

e         hbprca@meetingsfirst.com.au

w         www.hbprca.com.au





HBPRCA would like to acknowledge the ongoing support of the following sponsors:







Society for Endocrinology BES 2007

5 – 8 May 2007


Click here for meeting website

8th International Conference of Nuclear Cardiology - ICNC8

29 April – 2 May 2007

Prague - Czech Republic

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7th BHS Clinical Education Meeting for Primary Care

20 April 2007

Royal College of Physicians, London

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XVIIth Scientific Sessions of the Inter-American Society of Hypertension (IASH)

6 – 10 May 2007

Miami Beach, Florida, USA

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Lipids in Clinical Medicine Section: Obesity and adipose tissue biology

10 May 2007
The Royal School of Medicine, London

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American Society of Hypertension

19 – 23 May 2007

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Lindon Wing Festschrift

24 – 15 May 2007

Adelaide, Australia

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Metabolic Syndrome: fatty livers and arteries
7 June 2007

Royal College of Physicians, London

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Heart Failure 2007

9– 12 June 2007

Hamburg - Germany

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17th European Meeting on Hypertension

15 – 19 June 2007


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Europace 2007

24 – 27 June 2007

Lisbon – Portugal

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H.E.A.R.T UK 21st Annual Medical & Scientific Meeting

27 – 29 June 2007


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Key Advances in the Management of Hypertension (joint RSM/BHS Meeting)

4 July 2007
Royal Society of Medicine, London

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ESC Congress 2007

1 – 5 September 2007

Vienna – Austria

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Annual Scientific Meeting of the British Hypertension Society
24 – 26 September 2007
St. John’s College, Cambridge

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61st High Blood Pressure Research Conference 2007

26 – 29 September 2007

Tucson, AZ, USA

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2007 Cardiometabolic Health Congress

27 – 29 September 2007

Boston, MA, USA

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High Blood Pressure Research Council of Australia’s Annual Scientific Meeting

5 – 7 December 2007

Adelaide, South Australia

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2nd International Conference on Hypertension, Lipids, Diabetes and Stroke Prevention

6 – 8 March 2008

Prague, Czech Republic

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ISH 2008 – The 22nd Scientific Meeting of the International Society of Hypertension

14 – 19 June 2007

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Annual Scientific Meeting of the British Hypertension Society
24 – 26 September 2007
Queen’s College, Cambridge

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2nd International Symposium on Pheochromocytoma

17 – 20 September 2007
Queens College, Cambridge

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