Author- Dr. Md. Shamim, MD.
Vasomotor Reversal of Dale is a phenomenon demonstrating the effect of Epinephrine or Adrenaline on ß2 receptors on blood vessels after blocking ɑ1 effect, leading to severe fall in Blood Pressure. This phenomenon is first demonstrated by English Pharmacologist Sir Henry Dale.
Types of Adrenergic receptors in CVS
Effects of Epinephrine on Blood Pressure
Effect of Epinephrine (Adrenaline) on Adrenergic receptors in Blood Vessels
- Epinephrine acts all receptors- ɑ1, ɑ2, ß1 & ß2
- ɑ1 Leads vasoconstriction, whereas ß2 causes vasodilatation.
- At higher concentration of Epinephrine, it acts on both ɑ1 & ß2 receptors but action on ɑ1 receptor is predominating, leading to increase in Blood Pressure.
- At lower concentration of Epinephrine, it acts on only ß2 receptor because ß2 is more sensitive than ɑ1, so only action on ß2 receptors occurs, this leads to decrease in Blood Pressure.
Vasomotor Reversal of Dale
- First Epinephrine was administered through IV route.
- When Epinephrine at higher concentration in blood, leading to increase in Blood Pressure due to ɑ1 effect.
- After sometime metabolism started and concentration of epinephrine falling in blood, leading to decrease in blood pressure due to ß2 effect.
- This response is called Biphasic Response, which is normal.
- After blocking the ɑ1 receptor by nonselective ɑ blocker like Phentolamine.
- Again, Epinephrine is administered leading to severe fall in Blood Pressure due to ß2
- This Phenomenon is called Vasomotor Reversal of Dale, because we expect that after administration of epinephrine Blood Pressure should rise rather than fall.
- This phenomenon is first demonstrated by English Pharmacologist Sir Henry Dale, that is why this phenomenon is called Vasomotor reversal of Dale.
Vasomotor Re-reversal
- After demonstrating the normal biphasic response of Epinephrine (Adrenaline), ß2 receptor is blocking by nonselective ß-Blocker like propranolol.
- Again, Epinephrine is administered, leading to severe rise in Blood Pressure due to unopposed ɑ1
- This phenomenon is called Vasomotor Re-reversal, because it reverses the effect demonstrated on Vasomotor reversal of Dale.
Clinical Importance of Vasomotor reversal of Dale
- Clinical Importance of Vasomotor reversal of Dale is seen in Pheochromocytoma.
- In Pheochromocytoma severe hypertension occurs due to secretion of large amount of norepinephrine & epinephrine by stimulation of ɑ1
- In case of Epinephrine secreting pheochromocytoma if ɑ1 blocker drug like Prazosin is given as antihypertensive, causes severe fall in Blood Pressure and patient may go in severe shock.
- So ɑ1 blocker alone is contraindicated.
- In this case if nonselective ß-Blocker like Propranolol alone is given as treatment, causes severe rise in Blood Pressure and patient may go in Hypertensive crisis or Intracranial Hemorrhage.
- So nonselective ß-Blocker alone is also contraindicated.
- So, treatment of choice of Epinephrine secreting pheochromocytoma is drugs having both ɑ & ß blocker properties like Labetalol.
Pheochromocytoma
- Pheochromocytomas are an adrenal medullary tumor that secretes large amounts of norepinephrine & epinephrine and causes severe hypertension (hypertensive crisis).
- These are non-malignant tumor of adrenal medulla. They occur in 1 of every 1,000 patients with hypertension.
- These tumors are highly vascular and secreting high concentrations of norepinephrine and epinephrine, in a continuous or paroxysmal fashion.
- The peak age of onset is 40 years.
- Symptoms may be intermittent or continuous and include headache, anxiety, sweating, rapid breathing, and tachycardia.
- The diagnosis is established by abdominal imaging and measurement of urinary catecholamines and vanillylmandelic acid.
Conclusion of Vasomotor reversal of Dale
At the end of discussion, we conclude that Vasomotor reversal of Dale phenomenon having a great role in the pharmacotherapy of Pheochromocytoma especially Epinephrine secreting tumor. As we know Pheochromocytoma is a life-threatening condition. So before starting the antihypertensive drugs we should kept in mind about Pheochromocytoma. It is necessary to ruled out pheochromocytoma by abdominal imaging and measurement of urinary catecholamines and vanillylmandelic acid. In this way we can prevent unwanted complications during treatment.
References
- Current Medical Diagnosis and Treatment
- Harrison’s Principle of Internal Medicine
- Basic and Clinical Pharmacology, Katzung
- Vasomotor reversal of Dale
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