Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes.
BACKGROUND
Neurogenic orthostatic hypotension (OH) characterizes pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. We used neuropharmacologic probes that might distinguish these diseases based on loss of sympathetic noradrenergic nerves in PAF and PD + OH but not in MSA, and related the results to neurochemical and neuroimaging findings in the same patients.


METHODS
Patients with neurogenic OH (PD + OH; N = 35), MSA (N = 41), and PAF (N = 12) received iv trimethaphan (TRI), which inhibits sympathetic nerve traffic, or yohimbine (YOH), which stimulates sympathetic traffic. Dependent measures included blood pressure, plasma norepinephrine (NE) levels, and interventricular septal myocardial radioactivity after iv injection of the sympathoneural imaging agent, 6-[F]fluorodopamine.


RESULTS
The PD + OH and PAF groups had smaller pressor responses to YOH (12 +/- 8 and 13 +/- 1 mm Hg) and depressor responses to TRI (-14 +/- 8 and -17 +/- 7 mm Hg) than did the MSA group (43 +/- 8 mm Hg, -57 +/- 8 mm Hg; P = 0.01, P = 0.03). The PD + OH and MSA groups did not differ in NE responses to YOH and TRI. The depressor response to TRI, the pressor response to YOH, and the blood pressure difference between YOH and TRI all correlated positively with myocardial 6-[F]fluorodopamine-derived radioactivity.


CONCLUSIONS
The PD + OH resembles PAF and differs from MSA in hemodynamic responses to drugs that alter NE release from sympathetic nerves. The results fit with sympathetic noradrenergic denervation in PD + OH and PAF but not in MSA.
Sharabi
Yehonatan
Y
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA. sharabiy@ninds.nih.gov
Eldadah
Basil
B
Li
Sheng-Ting
ST
Dendi
Rhaguveer
R
Pechnik
Sandra
S
Holmes
Courtney
C
Goldstein
David S
DS
D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000175:diagnosis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism; D012791:Shy-Drager Syndrome / Q000175:diagnosis* / Q000378:metabolism; D014294:Trimethaphan / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D014294:Trimethaphan