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(Hypertension. 2000;36:553.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Endogenous Circulating Sympatholytic Factor in Orthostatic Intolerance

Robert E. Shapiro; Bradford Winters; Mariesa Hales; Townsend Barnett; Debra A. Schwinn; Nick Flavahan; Dan E. Berkowitz

From the Department of Neurology (R.E.S.), College of Medicine, University of Vermont, Burlington; the Department Anesthesiology and Critical Care Medicine (B.W., D.E.B.) and Department of Pulmonary Medicine (M.H., T.B.), The Johns Hopkins Medical Institutions, Baltimore, Md; the Departments of Anesthesiology, Surgery, and Pharmacology (D.A.S.), Duke University Medical Center, Durham, North Carolina; and the Heart and Lung Institute (N.F.), The Ohio State University, Columbus, Ohio.

Correspondence to Dan E. Berkowitz, MD, Department of Anesthesiology and Critical Care Medicine, Tower 711, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287. E-mail dberkowi{at}jhmi.edu

Abstract—Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of ₁-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2 (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an ₁-selective antagonist radioligand ([¹²⁵I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the _1B subtype but not other AR subtypes (_1A and _1D). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to _1B ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient’s syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of ₁-ARs.

Key Words: receptors, adrenergic, alpha • hypotension • norepinephrine • baroreceptors • vascular diseases

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