Effects of yohimbine on plasma catecholamine levels in orthostatic hypotension related to Parkinson disease or multiple system atrophy.

Abstract

Different pathophysiological mechanisms may underly orthostatic hypotension (OH) observed in neurological degenerative disorders. The present study investigates the responses to the pharmacological activation of sympathetic pathways induced by yohimbine (0.2 mg/kg orally) through measurements of plasma catecholamine levels in parkinsonian patients with (n = 9) or without OH (n = 11), in patients with multiple system atrophy (MSA) plus OH (n = 9), and in controls (n = 6). Basal norepinephrine plasma levels in parkinsonian patients with OH (71 +/- 11 pg/ml) were significantly lower (p < 0.05) than in parkinsonian patients without OH (280 +/- 25 pg/ml) or in controls (259 +/- 48 pg/ml). In patients with MSA plus OH, basal catecholamine plasma levels were in the normal range (344 +/- 54 pg/ml). Yohimbine significantly increased norepinephrine (p < 0.05) but not epinephrine plasma levels in all groups. However, the increment obtained in parkinsonian patients with OH (+53 +/- 18 pg/ml) remained significantly lower (p < 0.05) than in parkinsonian patients without OH or in controls (+638 +/- 140 and +457 +/- 103 pg/ml, respectively) as well as in MSA plus OH (+633 +/- 142 pg/ml). Yohimbine failed to modify the blood pressure and heart rate at the dose used. The results suggest that the yohimbine test is useful to elucidate the site of the dysfunction of the efferent sympathetic pathways in these two conditions. In Parkinson disease with OH, the lesion is both central and postganglionnic, whereas in MSA it is only centrally located.