This Article Full Text Full Text (PDF) All Versions of this Article: 112/17/2611    most recent CIRCULATIONAHA.104.526764v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Medow, M. S. Articles by Stewart, J. M. Search for Related Content PubMed PubMed Citation Articles by Medow, M. S. Articles by Stewart, J. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE Related Collections Other diagnostic testing Autonomic, reflex, and neurohumoral control of circulation Endothelium/vascular type/nitric oxide

(Circulation. 2005;112:2611-2618.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome

From New York Medical College, Valhalla (M.S.M., J.M.S.), and University of Oregon, Eugene (C.T.M.).

Correspondence to Julian M. Stewart, MD, PhD, Department of Pediatrics and Physiology, The Center for Pediatric Hypotension, Suite 3050, 19 Bradhurst Ave, New York Medical College, Hawthorne, NY 10532. E-mail stewart{at}nymc.edu

Received November 30, 2004; revision received July 23, 2005; accepted August 2, 2005.

Background— One variant of postural tachycardia syndrome (POTS), designated low-flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation.

Methods and Results— To investigate the hypothesis that microvascular endothelial dysfunction produces decreased peripheral blood flow in low-flow POTS, we performed experiments using laser-Doppler flowmetry (LDF) combined with iontophoresis in 15 low-flow POTS patients, 17 normal-flow POTS patients, and 13 healthy reference volunteers varying in age from 14 to 22 years. We tested whether -adrenergic vasoregulation was impaired using iontophoretic delivery of tyramine, phentolamine, and bretylium followed by a norepinephrine dose response. We tested endothelial-dependent and -independent receptor-mediated vasodilation by measuring acetylcholine and sodium nitroprusside dose responses. We tested whether nitric oxide–dependent vasodilation was different in these groups by testing the local thermal hyperemic response to saline used as a reference compared with the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). Adrenergic and receptor-dependent cutaneous vasoregulation was similar for low-flow POTS, normal-flow POTS, and reference subjects. Thermal hyperemia produced distinctly different findings: there was marked attenuation of the nitric oxide–sensitive plateau during prolonged heating, which was insensitive to L-NAME in low-flow POTS subjects. The pattern of thermal hyperemia response in low-flow POTS subjects during saline administration resembled the pattern in reference subjects during L-NAME administration and was minimally affected by L-NAME.

Conclusions— The data suggest that flow-dependent nitric oxide release is reduced in low-flow POTS. This may account for local flow regulation abnormalities.

Key Words: blood flow • lasers • nitric oxide synthase • syncope • tachycardia

This article has been cited by other articles:

				J. M. Stewart, A. J. Ocon, D. Clarke, I. Taneja, and M. S. Medow Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome Hypertension, May 1, 2009; 53(5): 767 - 774. [Abstract] [Full Text] [PDF]

				A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schachinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, et al. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings Cardiovasc Res, November 1, 2008; 80(2): 165 - 174. [Abstract] [Full Text] [PDF]

				J. M. Stewart, I. Taneja, N. Raghunath, D. Clarke, and M. S. Medow Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H327 - H334. [Abstract] [Full Text] [PDF]

				J. M. Stewart, I. Taneja, J. Glover, and M. S. Medow Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H466 - H473. [Abstract] [Full Text] [PDF]

				O. Schmiedel, M. L. Schroeter, and J. N. Harvey Microalbuminuria in Type 2 diabetes indicates impaired microvascular vasomotion and perfusion Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3424 - H3431. [Abstract] [Full Text] [PDF]

				J. M. Stewart, M. S. Medow, C. T. Minson, and I. Taneja Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2161 - H2167. [Abstract] [Full Text] [PDF]

				J. M. Stewart, I. Taneja, and M. S. Medow Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1908 - H1917. [Abstract] [Full Text] [PDF]

				B. L. Houghton, J. R. Meendering, B. J. Wong, and C. T. Minson Nitric oxide and noradrenaline contribute to the temperature threshold of the axon reflex response to gradual local heating in human skin J. Physiol., May 1, 2006; 572(3): 811 - 820. [Abstract] [Full Text] [PDF]

				G. Jacob, E. M. Garland, F. Costa, C. M. Stein, H.-G. Xie, R. M. Robertson, I. Biaggioni, and D. Robertson {beta}2-Adrenoceptor Genotype and Function Affect Hemodynamic Profile Heterogeneity in Postural Tachycardia Syndrome Hypertension, March 1, 2006; 47(3): 421 - 427. [Abstract] [Full Text] [PDF]