Published Online
on April 30, 2008

A more recent version of this article appeared on June 1, 2008

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Original Article

Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with the postural tachycardia syndrome

Elisabeth Lambert¹, Nina Eikelis, Murray Esler, Tye Dawood, Markus Schlaich, Richard Bayles, Florentia Socratous, Alex Agrotis, Garry Jennings, Gavin Lambert and Gautam Vaddadi

Baker Heart Research Institute

Correspondence: ¹ E-mail: elisabeth.lambert{at}baker.edu.au

Background—Clinical observations in patients with Postural Tachycardia syndrome (POTS) suggest an abnormal sympathetic nervous system activity and a dysfunction of the norepinephrine (NE) transporter (NET).

Methods and Results—We examined sympathetic nervous system responses to head–up tilt by combining NE plasma kinetics measurements and muscle sympathetic nerve activity (MSNA) recording and by quantifying NET protein content in peripheral sympathetic nerves in POTS patients compared with controls. POTS patients had elevated heart rate (HR) during supine rest [81±2 bpm vs 66±2 bpm in healthy subjects (HS), P<0.01]. Head–up tilt to 40° induced a greater rise in HR in the POTS patients (+24±4 bpm vs +13±2 bpm in HS, P<0.001). During supine rest, MSNA, arterial NE concentration and whole body NE spillover to plasma were similar in both groups. MSNA response to head-up tilt was greater in the POTS group (+29±3 bursts per min in POTS patients and +13±2 bursts per min in HS, P<0.001) but the NE spillover rise was similar in both groups (51% in the POTS subjects and 50% in the HS). Western blot analysis of NET protein extracted from forearm vein biopsies in POTS patients and HS demonstrated decreased expression of NET protein in POTS.

Conclusion—POTS patients exhibit decreased NET protein in their peripheral sympathetic nerves. Paradoxically, whole body NE spillover to plasma during supine rest and in response to head–up tilt is not altered despite excessive nerve firing rate in response to the head–up tilt.

Key Words: nervous system, sympathetic • norepinephrine • tachycardia

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