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Sympathetically mediated hypertension in autonomic failureBACKGROUND: Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could be driven by residual sympathetic activity. METHODS AND RESULTS: In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg. min; P=0.022). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+/-9.5%, respectively (P=0. 0015). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan were correlated (r=0.98; P=0.001). CONCLUSIONS: Residual sympathetic activity drives supine hypertension in MSA. It contributes to, but does not completely explain, supine hypertension in PAF.
Document ID
20040141534
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Shannon, J. R.
(Vanderbilt University Nashville, TN 37232-2195, United States)
Jordan, J.
Diedrich, A.
Pohar, B.
Black, B. K.
Robertson, D.
Biaggioni, I.
Roberton, D.
Date Acquired
August 22, 2013
Publication Date
June 13, 2000
Publication Information
Publication: Circulation
Volume: 101
Issue: 23
ISSN: 0009-7322
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: 1UO1 NS 33460
CONTRACT_GRANT: 1PO1 HL56693
CONTRACT_GRANT: RR00095
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Regulatory Physiology
Clinical Trial

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