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 neuro-imaging 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-18]fluorodopamine. Results: The PD + 011 and PAF groups had smaller pressor responses to YOH (12 divided by 8 and 13 +/- 1 mm Hg) and depressor responses to TRI (- 14 +/- 8 and - 17 +/- 7 nim Hg) than did the MSA group (43 +/- 8 min Hg, - 57 divided by 8 nun 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-18]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.