Published online before print November 10, 2003, doi: 10.1161/01.HYP.0000103160.35395.9E
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(Hypertension. 2004;43:169.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Sympathetic Augmentation in Hypertension
Role of Nerve Firing, Norepinephrine Reuptake, and Angiotensin Neuromodulation
From the Department of Medicine IV, University of Erlangen-Nuernberg (M.P.S.), Erlangen, Germany; and Baker Heart Research Institute and Cardiovascular Medicine, Alfred Hospital (E.L., D.M.K., Z.K., G.L., J.H., A.A., M.D.E.), and St Vincent’s Institute of Medical Research and Department of Medicine, University of Melbourne (D.J.C.), Melbourne, Australia.
Correspondence to Dr Markus P. Schlaich, Department of Medicine IV, University of Erlangen-Nuernberg, Krankenhausstr 12, 91054 Erlangen, Germany. E-mail markus.schlaich{at}baker.edu.au
There is growing evidence that essential hypertension is commonly neurogenic and is initiated and sustained by sympathetic nervous system overactivity. Potential mechanisms include increased central sympathetic outflow, altered norepinephrine (NE) neuronal reuptake, diminished arterial baroreflex dampening of sympathetic nerve traffic, and sympathetic neuromodulation by angiotensin II. To address this issue, we used microneurography and radiotracer dilution methodology to measure regional sympathetic activity in 22 hypertensive patients and 11 normotensive control subjects. The NE transport inhibitor desipramine was infused to directly assess the potential role of impaired neuronal NE reuptake. To evaluate possible angiotensin sympathetic neuromodulation, the relation of arterial and coronary sinus plasma concentrations of angiotensin II to sympathetic activity was investigated. Hypertensive patients displayed increased muscle sympathetic nerve activity and elevated total systemic, cardiac, and renal NE spillover. Cardiac neuronal NE reuptake was decreased in hypertensive subjects. In response to desipramine, both the reduction of fractional transcardiac 3[H]NE extraction and the increase in cardiac NE spillover were less pronounced in hypertensive patients. DNA sequencing analysis of the NE transporter gene revealed no mutations that could account for reduced transporter activity. Arterial baroreflex control of sympathetic nerve traffic was not diminished in hypertensive subjects. Angiotensin II plasma concentrations were similar in both groups and were not related to indexes of sympathetic activation. Increased rates of sympathetic nerve firing and reduced neuronal NE reuptake both contribute to sympathetic activation in hypertension, whereas a role for dampened arterial baroreflex restraint on sympathetic nerve traffic and a peripheral neuromodulating influence of angiotensin II appear to be excluded.
Key Words: hypertension, essential • catecholamines • sympathetic nervous system • norepinephrine • angiotensin II
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