Oral yohimbine in human autonomic failure

Onrot, Jack; Goldberg, Michael R.; Biaggioni, Italo; Wiley, Ronald G.; Hollister, Alan S.; Robertson, David L.

doi:10.1212/wnl.37.2.215

Cited by 85 publications

(34 citation statements)

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“…Previous studies have not separately considered the unusual situation of MSA lacking OH. Overall, in MSA it has been proposed that supine hypertension reflects increased sympathetic neurovascular tone, because the patients have excessive depressor responses to ganglion blockade produced by intravenous trimethaphan, 2 which reduces NE release from sympathetic nerve terminals, and excessive pressor responses to ␣ 2 -adrenoceptor blockade produced by intravenous yohimbine, 34 which increases NE release from the terminals. Although the present study was not designed to test this concept, the finding of lower, not higher, plasma NE levels in MSAϩOH than in MSA lacking OH does not seem to fit well with the notion of increased release of NE from intact sympathetic nerve terminals as the explanation for supine hypertension in MSA.…”

Section: Discussionmentioning

confidence: 99%

Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure

et al. 2003

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Abstract-Supine hypertension occurs commonly in primary chronic autonomic failure. This study explored whether supine hypertension in this setting is associated with orthostatic hypotension (OH), and if so, what mechanisms might underlie this association. Supine and upright blood pressures, hemodynamic responses to the Valsalva maneuver, baroreflex-cardiovagal gain, and plasma norepinephrine (NE) levels were measured in pure autonomic failure (PAF), multiple-system atrophy (MSA) with or without OH, and Parkinson's disease (PD) with or without OH. Controls included age-matched, healthy volunteers and patients with essential hypertension or those referred for dysautonomia. Baroreflex-cardiovagal gain was calculated from the relation between the interbeat interval and systolic pressure during the Valsalva maneuver. PAF, MSA with OH, and PD with OH all featured supine hypertension, which was equivalent in severity to that in essential hypertension, regardless of fludrocortisone treatment. Among patients with PD or MSA, those with OH had higher mean arterial pressure during supine rest (109Ϯ3 mm Hg) than did those lacking OH (96Ϯ3 mm Hg, Pϭ0.002). Baroreflex-cardiovagal gain and orthostatic increments in plasma NE levels were markedly decreased in all 3 groups with OH. Among patients with PD or MSA, those with OH had much lower mean baroreflex-cardiovagal gain (0.74Ϯ0.10 ms/mm Hg) than did those lacking OH (3.13Ϯ0.72 ms/mm Hg, Pϭ0.0002). In PAF, supine hypertension is linked to both OH and low baroreflex-cardiovagal gain. The finding of lower plasma NE levels in patients with than without supine hypertension suggests involvement of pressor mechanisms independent of the sympathetic nervous system. Key Words: hypertension, essential Ⅲ hypotension Ⅲ Parkinson's disease Ⅲ autonomic nervous system Ⅲ sympathetic nervous system Ⅲ norepinephrine P rimary chronic autonomic failure has been classified clinically into 3 forms: pure autonomic failure (PAF), multiple-system atrophy (MSA), and autonomic failure in the setting of Parkinson's disease (PD). 1 All 3 forms typically include orthostatic hypotension (OH), wherein reflexive increases in sympathetic neurocirculatory tone fail to compensate adequately for decreased venous return to the heart.Patients with primary chronic autonomic failure also often have supine hypertension. 2 Because of widespread use of the salt-retaining steroid fludrocortisone to treat OH and literature documenting increases in blood pressure secondary to mineralocorticoid administration, 3,4 supine hypertension in primary chronic autonomic failure might be a side effect of treating the OH and not part of the disease; however, supine hypertension has been reported in a substantial proportion of untreated patients. 5 Analogously, levodopa is a mainstay in the treatment of PD, and based on literature that levodopa produces OH, 6 OH in PD might be a side effect of treating the movement disorder and not part of the disease; however, OH occurs in at least some patients with PD who are off or have never been ...

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Section: Discussionmentioning

confidence: 99%

Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure

et al. 2003

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“…12 Yohimbine substantially increases blood pressure in a large subgroup of autonomic failure patients. 12,21,22 It does not elicit a pressor response during ganglionic blockade in normal controls. 23 In contrast, clonidine, an ␣2-adrenergic agonist, decreases blood pressure in some autonomic failure patients and can increase blood pressure in others.…”

Section: Discussionmentioning

confidence: 94%

The Pressor Response to Water Drinking in Humans

Jordan¹,

Shannon²,

Black³

et al. 2000

Circulation

328

454

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Background-Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. Methods and Results-We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33Ϯ5 mm Hg in MSA and 37Ϯ7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11Ϯ2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. Conclusions-Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

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“…In addition, orthostatic hypotension has been treated with yohimbine both in the setting of multi-system atrophy (Onrot et al, 1987) and in Parkinson's disease (Montastruc et al, 1981). The "freezing" phenomena that accompanies Parkinson's disease may also result from a NE deficit (Narabayashi, 1983) and might respond to treatment with yohimbine.…”

Section: Discussionmentioning

confidence: 99%

Effect of yohimbine on brain monoamines: An in vivo study

Brannan

Martinez-Tica

Yahr

1991

J Neural Transm Gen Sect

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Following the administration of yohimbine, an alpha 2-adrenoreceptor antagonist, the levels of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) increased significantly in the lateral ventricular fluid of rats. These increases were abolished when animals were pretreated with alpha-methyl-para-tyrosine or reserpine. Dopamine (DA) was not detected in ventricular fluid either before or after yohimbine administration. Yohimbine administration did, however, increase intracellular DA levels in the corpus striatum. These findings indicate that yohimbine promotes NE and DA release in the brain and suggest that it also modifies the activity of the serotonin system.

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Oral yohimbine in human autonomic failure

Cited by 85 publications

References 0 publications

Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure

Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure

The Pressor Response to Water Drinking in Humans

Effect of yohimbine on brain monoamines: An in vivo study

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