Neurogenic orthostatic hypotension: Roles of norepinephrine deficiency in its causes, its treatment, and future research directions

Adam Loavenbruck, Paola Sandroni

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations


Background:Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change.Research design and methods:PubMed searches with orthostatic hypotension and norepinephrine as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research.Results:Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinsons disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa.Conclusions:Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively targeting orthostatic blood-pressure decreases.

Original languageEnglish (US)
Pages (from-to)2095-2104
Number of pages10
JournalCurrent Medical Research and Opinion
Issue number11
StatePublished - Nov 2 2015

Bibliographical note

Funding Information:
Editorial support for this review was funded by Lundbeck LLC.

Publisher Copyright:
© 2015 Taylor & Francis.


  • Blood pressure
  • Droxidopa
  • Homeostasis
  • Midodrine
  • Norepinephrine
  • Orthostatic hypotension
  • Parkinson's disease
  • Pressor agents


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