Idiopathic orthostatic hypotension from failure of noradrenaline release in a patient with vasomotor innervation.

Abstract

SUMMARY A 26 year old man is described with life-long orthostatic hypotension unrelated to autonomic nerve degeneration and apparently due to failure of peripheral noradrenaline release. Tests of parasympathetic and sympathetic cholinergic nerve function were normal, but sympathetic adrenergic activity was defective. Thus blood pressure regulation was abnormal. There was no pressor response to tyramine, an indirect sympathomimetic drug, but a marked pressor response to the directly acting sympathomimetic drugs phenylephrine and noradrenaline. On standing there was a progressive fall rather than a rise in circulating noradrenaline concentrations, although adrenaline levels rose normally. The pupils showed diminished responses to ephedrine and cocaine, and a normal response to phenylephrine. Fluorescence microscopy of blood vessels showed that they were innervated with adrenergic nerves. His orthostatic hypotension responded well to oral phenylephrine (50 mg five times daily) but not to other forms of therapy. It is suggested that this patient's symptoms were due to failure of noradrenaline release even though sympathetic adrenergic nerves were present. We therefore wish to draw attention to a further cause of orthostatic hypotension, failure ofperipheral noradrenaline release without autonomic neuropathy.Orthostatic hypotension may occur either as an idiopathic disorder or as a complication of many neurological disorders Spalding, 1974, 1976

Which drug for which orthostatic hypotension?

“…The failure of the autonomic nervous system is mainly due to peripheral sympathetic neuron degeneration (Dotson et al, 1990) associated with a decreased catecholamine fluorescence from nerve endings (Kontos et al, 1975;Rubinstein et al, 1978). The postganglionic nature of the disturbance was further supported by the existence of low plasma catecholamine levels (Ziegler et al, 1977;Polinsky et al, 1981;Goldstein et al, 1989) and the failure of tyramine to increase noradrenaline (Nanda et al, 1977;Polinsky et al, 1981).…”