Antidiuretic hormone (ADH), also known as vasopressin, is a peptide hormone that plays a key role in regulating blood pressure and fluid balance in the body. ADH is synthesized in the hypothalamus and released from the posterior pituitary gland. It acts on the kidneys and blood vessels to control water retention and vascular tone.
Overview of ADH
ADH is a 9-amino acid peptide hormone that is encoded by the AVP gene. It is packaged into neurosecretory vesicles in neurons in the hypothalamus and transported down axons to the posterior pituitary gland, where it is stored until released into circulation.
The main triggers for ADH release are:
- Increased plasma osmolality – This signals a state of dehydration
- Decreased blood volume/pressure – Detected by baroreceptors in blood vessels
Once released, ADH binds to specific receptors (V2 receptors) in the collecting ducts of the kidneys and stimulates aquaporin channels, causing increased water reabsorption back into the bloodstream. This concentrates the urine and conserves water in the body.
ADH also binds to V1a receptors on vascular smooth muscle cells, inducing vasoconstriction. This causes increased systemic vascular resistance and helps elevate blood pressure.
Therefore, ADH coordinates changes in blood volume, osmolality, and blood pressure by acting at the kidneys to control water balance and at blood vessels to control vascular tone.
Regulation of ADH Release
There are several key factors that regulate the synthesis and release of ADH:
Plasma Osmolality
One of the main stimuli for ADH release is increased osmolality of the blood, indicating dehydration or water loss. Specialized osmoreceptor neurons in the hypothalamus monitor sodium concentration in the blood. An elevation in sodium concentration causes these neurons to trigger ADH release.
ADH then acts in the kidneys to concentrate the urine and conserve water, diluting the blood back towards normal osmolality. This osmoregulatory system maintains tight control of plasma osmolality around 280-290 mOsm/kg.
Blood Volume and Pressure
ADH release is also stimulated by a fall in blood volume or arterial pressure, which is detected by baroreceptors in the carotid sinus, aortic arch, and atria. Hypovolemia signals a state of dehydration and prompts ADH release to retain water in the body and expand blood volume.
Conversely, an increase in blood volume suppresses ADH release through the baroreceptor reflex. Atrial stretch receptors detect increased blood volume and inhibit ADH secretion.
Stress and Anxiety
The sight of blood or situations causing pain or emotional distress can trigger ADH release through the sympathetic nervous system. This is why stressful events can sometimes cause urinary retention.
Circadian Rhythm
ADH secretion follows a circadian rhythm, with highest levels in the early morning that decrease throughout the daytime. This contributes partly to the need to urinate frequently in mornings and helps conserve water while sleeping at night.
Drugs and Hormones
Certain medications like NSAIDs, antidepressants, and opioids can induce ADH release. Anti-diuretic drugs like desmopressin directly act like ADH.
Estrogen may enhance ADH secretion, while alcohol suppresses secretion. This explains increased urination with drinking alcohol due to reduced ADH action.
Mechanism of ADH Action
ADH elicits its effects on blood pressure and body water balance by interacting with specific receptors found in the kidneys and blood vessels:
Kidney Collecting Ducts
In the kidney collecting ducts, ADH binds mainly to V2 receptors on the basolateral membrane of epithelial cells. This stimulates signaling pathways that cause insertion of aquaporin-2 water channels in the apical membrane.
Aquaporins allow passive movement of water from the tubule into the interstitial space in response to the osmotic gradient generated by the renal countercurrent multiplier system. This concentrates the urine and retains water in the body.
Vascular Smooth Muscle
ADH binds to V1a receptors on smooth muscle cells of peripheral blood vessels, especially arteries. This activates a G-protein signaling cascade that elevates intracellular calcium levels.
Calcium stimulates muscle contraction and vasoconstriction. This increases systemic vascular resistance and blood pressure.
ADH and Blood Pressure Regulation
ADH is a powerful regulator of blood pressure due to its vasoconstrictive effects on vascular smooth muscle:
- ADH increases blood pressure through V1a receptor-mediated vasoconstriction.
- It increases blood volume by retaining water in the body.
- ADH opposes the actions of atrial natriuretic peptide (ANP), which is natriuretic and vasodilatory.
Under normal conditions, ADH maintains basal vascular tone and blood pressure while also preserving fluid balance. However, excess ADH release or activity can lead to hypertension in conditions like:
SIADH
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by persistently elevated ADH levels. This leads to water retention, hyponatremia, and diluted blood.
Although blood volume is expanded, the reduced osmolarity suppresses renin-angiotensin and sympathetic activity. Thus blood pressure is usually normal or only mildly elevated in SIADH.
Acute Stress
Pain, anxiety, trauma, or surgery can transiently increase ADH release and raise blood pressure. This hypertensive response is mediated by ADH and the sympathetic nervous system.
Chronic Stress
In situations of chronic stress, ADH secretion remains persistently elevated. The vasoconstrictive effects of ADH can contribute to stress-related hypertension over time.
Congestive Heart Failure
Advanced heart failure is characterized by very high ADH levels due to arterial underfilling and baroreceptor activation. The combination of ADH vasoconstriction and fluid overload significantly raises blood pressure.
Adrenal Insufficiency
When adrenal hormone output is low, there is reduced suppression of ADH release. Elevated ADH levels may raise blood pressure in adrenal insufficiency.
Clinical Uses of ADH
Synthetic ADH and its analogs have the following clinical uses:
Vasopressin
Vasopressin injection is used to manage acute hypotension and septic shock by exploiting its V1a receptor-mediated vasoconstriction. It rapidly elevates blood pressure in emergency situations like post-cardiac arrest.
Desmopressin
Desmopressin is a synthetic analog of ADH that retains antidiuretic effects with minimal vasoconstriction. It is used to treat central diabetes insipidus, primary nocturnal enuresis, and bleeding disorders like hemophilia and von Willebrand disease.
Terlipressin
Terlipressin is a prodrug of lysine vasopressin that has a longer duration of action. It is used to treat refractory hypotension in septic shock when standard vasopressors fail.
Diagnostic Testing
Measurement of copeptin, a stable surrogate marker for ADH release, has diagnostic utility in various conditions like diabetes insipidus, SIADH, and heart failure.
Conclusion
In summary, ADH is a key hormone that regulates both vascular tone and body water balance. It is released in response to increased plasma osmolality or decreased blood volume/pressure. ADH acts on the kidneys to concentrate urine and conserve water. It also induces vasoconstriction of peripheral blood vessels via V1a receptors, increasing blood pressure. Excess ADH activity can contribute to hypertension in several disorders. Synthetic ADH analogs are used clinically for disorders of fluid balance and to treat shock states. Careful regulation of ADH release and effects is necessary to maintain fluid and cardiovascular homeostasis.