Hypertension Controlling Blood Pressure without Drugs – Developing New Strategies Markus P Schlaich and Murray D Esler Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute and Heart Centre, Alfred Hospital, Melbourne
Abstract
Non-optimal blood pressure is the leading cause of death globally, and each year is responsible for seven million deaths. Current therapeutic strategies for hypertension are mainly based on lifestyle interventions and pharmacological approaches, but rates of blood pressure control remain unsatisfactory and additional options are required. In this context, novel device-based approaches specifically targeting the sympathetic nervous system as a major player in blood pressure control have recently been tested clinically with promising results. Device-based approaches may provide additional and more effective treatment of hypertension and its adverse consequences in the future.
Keywords Hypertension, sympathetic nervous system, cardiovascular, renal denervation, baroreflex
Disclosure: Markus P Schlaich and Murray D Esler are principal investigators in clinical trials sponsored by Ardian, Inc. (NCT00483808 and NCT00551304) and are both supported by senior research fellowships from the National Health and Medical Research Council (NHMRC) of Australia. Received: 8 April 2010 Accepted: 20 May 2010 Citation: European Cardiology, 2010;6(2):18–21 Correspondence: Markus P Schlaich, Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne Victoria 8008, Australia. E:
markus.schlaich@
bakeridi.edu.au
The pathogenesis of primary hypertension is multifactorial. However, the sympathetic nervous system plays an important role in circulatory and metabolic control and has clearly been established as a major contributor to the development of hypertension, with blood pressure elevation being initiated and sustained by elevated sympathetic nervous activity. Increased sympathetic outflow to the heart resulting in increased cardiac output and neurally mediated vasoconstriction of peripheral blood vessel are obvious examples of neural pathophysiological pathways leading to elevated blood pressure. The consequences of increased sympathetic outflow to the kidneys, perhaps most important in this context, are sodium and water retention, increased renin release and alterations of renal blood flow, effects that contribute substantially to blood pressure elevations both acutely and in the long term. Accordingly, targeting the sympathetic nervous system directly appears to be a logical therapeutic approach for the treatment of hypertension.
A Specific Role of Renal Nerves in Hypertension
The renal nerves are of particular importance in control of kidney function, volume homeostasis and blood pressure control. Using gold standard radiotracer methodology to investigate regional overflow of norepinephrine from the kidneys to plasma clearly demonstrated that renal norepinephrine spillover rates are markedly elevated in patients with essential hypertension1,2
and are associated
Interestingly, activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure,4
18
with hypertensive target organ damage such as left ventricular hypertrophy.3
a common
clinical consequence of long-term and sustained elevated blood pressure. Indeed, renal sympathetic activation has been shown to predict all-cause mortality and heart transplantation in patients with congestive heart failure.5
Similarly, elevated norepinephrine plasma
levels have been identified as major contributors to adverse cardiovascular outcomes in end-stage renal disease,6
another
condition commonly characterised by substantially elevated sympathetic nerve activity.7
The kidneys have a dense afferent sensory and efferent sympathetic innervation and are thereby strategically positioned to be the origin as well as the target of sympathetic activation.8
Renal sensory afferent
nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in cardiovascular control, such as the heart and peripheral blood vessels, by modulating posterior hypothalamic activity.9,10
Interestingly, abrogation of renal
sensory afferent nerves has been demonstrated to reduce both blood pressure and organ-specific damage caused by chronic sympathetic overactivity in various experimental models.11,12
Post-ganglionic sympathetic efferent nerve fibres innervate all essential renal structures including the renal vasculature, the tubules and the juxtaglomerular apparatus.13
The consequences of renal
sympathetic activation include volume retention and sodium reabsorption,14
renal blood flow reduction15,16 aldosterone system activation.17
Therapeutic efforts applying pharmacological principles to counteract the consequences of renal efferent sympathetic
© TOUCH BRIEFINGS 2010 and renin–angiotensin–
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