Boards may call this neurogenic orthostatic hypotension. Plain English: standing drops the blood pressure because the autonomic nerves fail to fire the Alpha-1 vessel squeeze.
Clinical Vignette · Boards Opener
A 60-year-old man has dizziness when standing. He fainted at work on a hot day. He also has constipation and erectile dysfunction. Lying BP is 130/70 with HR 60. Standing BP is 90/60 with HR 60.
Alpha-1 is the pressure rescue. Standing pulls blood into the legs. A healthy baroreflex increases sympathetic tone, norepinephrine hits Alpha-1 receptors on arterioles and veins, and vascular tone keeps blood in the brain. Here the BP falls and the HR stays flat, so the autonomic rescue failed.
Interactive Physiology
Stand up. Watch the reflex fail.
Orthostatic hypotension is a pressure drop after standing. When autonomic failure causes it, the heart rate barely rises because sympathetic outflow cannot deliver the Alpha-1 squeeze.
Brain perfusion: safe
Standing BP
130/70
Heart rate
60
Alpha-1 tone
low
Pick a physiology state, then watch what happens when the patient stands.
Standing Pressure Lock
Pressure drop
Standing systolic BP falls by at least 20 mm Hg or diastolic by at least 10 mm Hg within 3 minutes.
Trap
The diagnosis is not finished until you look at the HR response.
Autonomic move
BP falls, HR barely rises, and autonomic symptoms appear: constipation, urinary or erectile dysfunction, heat intolerance, sweating changes.
Receptor move
Alpha-1 on vascular smooth muscle is the missing constrictor signal.
Pattern Sorter
Vitals tell you where the failure lives.
The same complaint, "dizzy when standing," can be autonomic failure, dehydration, POTS, vasovagal syncope, primary adrenal insufficiency, or drug effect. Sort by BP, HR, electrolyte clues, skin findings, and the non-cardiac autonomic clues.
Autonomic failure
BP falls. HR response is blunted. Constipation, ED, urinary symptoms, anhidrosis, gastroparesis, or Parkinson/MSA clues can ride along.
Volume depletion
BP falls, but HR rises because the reflex arc works. Look for vomiting, diarrhea, bleeding, low intake, dry mucosa, high BUN:Cr.
POTS
HR jumps by at least 30 bpm after standing, but BP does not meet the orthostatic hypotension drop.
Primary adrenal insufficiency
Adrenal cortex failure causes salt and cortisol loss: hyperpigmentation, weight loss, abdominal pain, hyponatremia, hyperkalemia, and volume-driven orthostasis.
Challenge: A patient stands. BP drops from 138/76 to 96/58. HR changes from 62 to 64. He has urinary retention and erectile dysfunction. What is the pattern?
What changes first?
Standing pulls blood into the legs.
What should the HR do?
The heart rate should rise. In autonomic failure it stays blunted because sympathetic output cannot rescue the pressure.
What signal is missing?
Alpha-1 vessel squeeze is missing. Constipation, erectile dysfunction, urinary retention, sweating change, Parkinson disease, diabetes, amyloid, or MSA makes this pattern stick.
Lesion Ladder
What detects the stretch drop?
Carotid sinus and aortic arch baroreceptors travel by CN IX and CN X to the nucleus tractus solitarius.
Where is the signal integrated?
Brainstem autonomic centers increase sympathetic outflow and withdraw vagal tone.
Peripheral noradrenergic degeneration, diabetic autonomic neuropathy, Parkinson disease, pure autonomic failure, amyloid, or MSA can break the response.
Acetylcholine Bridge
ACh starts the autonomic message. NE usually squeezes the vessels.
This is the board connection: acetylcholine is used at the autonomic ganglion. The final vessel squeeze for standing pressure is usually norepinephrine on Alpha-1. Pyridostigmine helps because it increases ACh at the ganglion, upstream of that final Alpha-1 output.
1 / 5
Tap the transmitter
Ganglion relay: Preganglionic sympathetic and parasympathetic neurons release ACh onto nicotinic Nn receptors. That is why ACh still matters in an autonomic-failure page even when the final pressure receptor is Alpha-1.
Drug Mechanism Lock
Treat the missing pressure signal.
First remove offenders and add water, salt, compression, slow standing, and head-of-bed elevation. Boards most often test the drug by what it replaces: Alpha-1 vessel tone, volume, or ganglionic acetylcholine signaling.
Midodrine: direct Alpha-1 rescue
Midodrine is converted to an active Alpha-1 agonist. Alpha-1 squeezes arteriolar and venous smooth muscle, raises standing BP, and treats symptomatic orthostatic hypotension from autonomic failure.
Alpha-1 agonist familyThese drugs mimic the vascular side of epinephrine/norepinephrine: Alpha-1 receptor stimulation on vascular smooth muscle uses Gq signaling, raises intracellular calcium, contracts arterioles and veins, increases systemic vascular resistance, and raises BP.
Same receptor, different location
Phenylephrine: IV Alpha-1 agonism contracts vascular smooth muscle, increases systemic vascular resistance, and raises blood pressure during acute hypotension.
Autonomic nerves are the pressure-control wiring, not just a heart-rate number.Baroreceptors detect low stretch; sympathetic output should restore vessel tone.Adrenal insufficiency is a different orthostasis route: aldosterone and cortisol failure.
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Question 1Autonomic failure bank
Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last reviewed June 2026
