title: Neurogenic orthostatic hypotension: roles of norepinephrine deficiency in its causes, its treatment, and future research directions.
abstract: 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.
  
  
  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, Parkinson's 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.
authors.affiliation: a a Department of Neurology , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Loavenbruck
authors.affiliation: b b Department of Neurology , Mayo Clinic , Rochester , MN , USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sandroni
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000503:physiopathology* / Q000628:therapy; D001794:Blood Pressure / Q000187:drug effects; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency*; D015103:Droxidopa / Q000008:administration & dosage; D006801:Humans; D007024:Hypotension, Orthostatic / Q000503:physiopathology* / Q000628:therapy; D009638:Norepinephrine / Q000172:deficiency*; D012106:Research / Q000639:trends
chemical_list: D004299:Dopamine beta-Hydroxylase; D015103:Droxidopa; D009638:Norepinephrine
keywords: Blood pressure; Droxidopa; Homeostasis; Midodrine; Norepinephrine; Orthostatic hypotension; Parkinson’s disease; Pressor agents