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(Circulation. 2005;111:1574-1582.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Renin-Aldosterone Paradox and Perturbed Blood Volume Regulation Underlying Postural Tachycardia Syndrome

Satish R. Raj, MD; Italo Biaggioni, MD; Paula C. Yamhure, RN; Bonnie K. Black, RN, NP; Sachin Y. Paranjape, BS; Daniel W. Byrne, MS; David Robertson, MD

From the Divisions of Clinical Pharmacology (S.R.R., I.B., D.R.) and Cardiovascular Medicine (P.C.Y., B.K.B., S.Y.P.), Departments of Medicine, Pharmacology (S.R.R., I.B., D.R.), Biostatistics (D.W.B.), and Neurology (D.R.), Vanderbilt University, Nashville, Tenn.

Reprint requests to Satish R. Raj, MD, AA3228 Medical Center North, Vanderbilt University, 1161 21st Ave S, Nashville, TN 37232-2195. E-mail satish.raj{at}vanderbilt.edu

Received September 26, 2004; revision received December 14, 2004; accepted December 21, 2004.

Background— Patients with postural tachycardia syndrome (POTS) experience considerable disability, but in most, the pathophysiology remains obscure. Plasma volume disturbances have been implicated in some patients. We prospectively tested the hypothesis that patients with POTS are hypovolemic compared with healthy controls and explored the role of plasma renin activity and aldosterone in the regulation of plasma volume.

Methods and Results— Patients with POTS (n=15) and healthy controls (n=14) underwent investigation. Heart rate (HR), blood pressure (BP), plasma renin activity, and aldosterone were measured with patients both supine and upright. Blood volumes were measured with ¹³¹I-labeled albumin and hematocrit. Patients with POTS had a higher orthostatic increase in HR than controls (51±18 versus 16±10 bpm, P<0.001). Patients with POTS had a greater deficit in plasma volume (334±187 versus 10±250 mL, P<0.001), red blood cell volume (356±128 versus 218±140 mL, P=0.010), and total blood volume (689±270 versus 228±353 mL, P<0.001) than controls. Despite the lower plasma volume in patients with POTS, there was not a compensatory increase in plasma renin activity (0.79±0.58 versus 0.79±0.74 ng · mL^–1 · h^–1, P=0.996). There was a paradoxically low level of aldosterone in the patients with POTS (190±140 pmol/L versus 380±230 pmol/L; P=0.017).

Conclusions— Patients with POTS have paradoxically unchanged plasma renin activity and low aldosterone given their marked reduction in plasma volume. These patients also have a significant red blood cell volume deficit, which is regulated by the renal hormone erythropoietin. These abnormalities suggest that the kidney may play a key role in the pathophysiology of POTS.

Key Words: tachycardia • renin • nervous system, autonomic • blood volumealdosterone

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