It is a nano peptide (nine amino acids) synthesized in the hypothalamus, transported, and stored in the posterior lobe of the pituitary gland that releases it into the bloodstream.
The antidiuretic hormone, ADH, also called vasopressin and arginine-vasopressin, has antidiuretic and vasopressor actions.
Vasopressin is a nano peptide with a disulfide bond between two cysteine residues. Its structure resembles that of oxytocin.
Formed in the supraoptic and paraventricular nuclei of the hypothalamus by cleavage of a 168 amino acid preprohormone and then a prohormone, vasopressin is transported to the posterior lobe of the pituitary gland that stores it.
Its release depends mainly on hyperosmolality and blood volume and, in addition, on the effects of certain medications.
The increase in the osmolality of the blood supplying the hypothalamic-pituitary complex causes vasopressin secretion. Patients with central diabetes insipidus have no response to increased osmolality.
The decrease in the volume of extracellular fluids and blood pressure decreases the stimulation of the baroreceptors located in the atria, pulmonary veins, and carotid sinus, increasing vasopressin secretion, which has opposite effects. In addition, angiotensin facilitates the secretion of ADH;
Effects of medications
Tricyclic antidepressants, fluoxetine, other serotonin reuptake inhibitors, nicotine, neuroleptics, and carbamazepine can increase ADH secretion. When this increase is significant, it results in fluid retention, usually detected by dilution hyponatremia.
This syndrome is referred to in the literature as SIADH or syndrome of inappropriate antidiuretic hormone secretion.
Other medications such as phenytoin, mineralocorticoids, and glucocorticoids can decrease secretion.
Ethanol also reduces it. Modifications of the effect of the hormone at the renal level can also be observed.
In patients with central diabetes insipidus, ADH is insufficient or has no secretion. In patients with nephrogenic diabetes insipidus, there is ADH secretion but no response at the renal level.
The plasma half-life of ADH is approximately 15 to 30 minutes. It is inactivated by plasma and tissue endopeptidases, particularly in the kidney and liver.
Effects of vasopressin
The effects of vasopressin result from the stimulation of receptors V1 and V2, V1 mainly responsible for vasoconstriction, and V2 for the antidiuretic effect.
The G protein couples the V1 receptors to phospholipase C. Their activation causes the hydrolysis of PIP2 in IP3 and DAG, which induces an increase in the intracellular calcium concentration, responsible for vasoconstriction.
V2 receptors are G protein-coupled to adenyl cyclase. Its activation causes an increase in cAMP, which, through protein kinases, induces the activation of aqueous channels called type 2 aquaporins or AQP2, located mainly in the renal collecting duct.
Under the influence of vasopressin, AQP2 migrates from the cytoplasm to the apical membrane. In nephrogenic diabetes insipidus, there are AQP2 alterations.
Antidiuretic action (V2)
ADH increases the water permeability of the collecting ducts in the cortical and medullary parts of the kidney.
It induces the incorporation of aquaporins in the apical membrane of the collecting ducts and their opening, allowing water reabsorption.
A certain number of medicines modify the activity of ADH in the kidney:
Chlorpropamide, acetaminophen, carbamazepine, indomethacin, and other non-steroidal anti-inflammatory drugs can increase ADH activity and cause fluid retention.
Chlorpropamide, a hypoglycemic sulfonamide, potentiates the action of low vasopressin concentrations.
When used for the treatment of diabetes mellitus, chlorpropamide can cause, as an adverse effect, an apparent syndrome of inappropriate ADH secretion.
In treating central diabetes insipidus, when ADH analogs cannot be used, chlorpropamide is used alone or sometimes in combination with a thiazide diuretic.
Lithium, demeclocycline, and methoxyflurane decrease the renal activity of ADH. The polyuria observed in some patients treated with lithium is explained by this mechanism.
Demeclocycline is the only tetracycline with an antagonistic effect on ADH in the kidney. Reduces water retention induced by excessive secretion of antidiuretic hormones, often of neoplastic origin. When used as an antibiotic, demeclocycline can cause nephrogenic diabetes insipidus with polyuria and polydipsia.
Phototoxic reactions can occur in patients treated with demeclocycline, and exposure to sunlight should be avoided.
Furthermore, thiazide diuretics have a paradoxical antidiuretic effect in patients with nephrogenic diabetes insipidus, probably due to sodium depletion in the tubular fluid. They are the primary treatment, often combined with amiloride, for nephrogenic diabetes insipidus.
Vasoconstrictor effect (V1)
ADH induces vasoconstriction at doses higher than those necessary to induce water retention. The plasma concentration of vasopressin may be sufficient to increase peripheral resistance and blood pressure.
The decrease in cutaneous blood flow observed in smokers could result from increased vasopressin secretion under the influence of nicotine.
The development of specific V1 antagonists would allow better specification of the role of vasopressin in physiology and pathology and probably find therapeutic applications.
Role in hemostasis:
ADH has a platelet aggregation effect under stress conditions where its secretion is significantly increased.
It has a favorable action in patients with hemophilia or von Willebrand disease by increasing the secretion of Factor VIII and Factor von Willebrand. Desmopressin is generally used in these indications, which decreases bleeding time.
ADH stimulates the secretion of ACTH.
Experimental studies showed that ADH facilitates memorization, while oxytocin could have an inverse effect.
Furthermore, by activating receptors in the brain, vasopressin is involved in sexual behavior, at least in certain animal species.
Structural analogs of vasopressin
The vasopressor effect is seldom desirable; vasopressin analogs such as desmopressin with vigorous antidiuretic activity and low vasopressor activity have been obtained. The following table compares the effects of vasopressin and desmopressin.
Desmopressin differs from vasopressin by losing the amine group in cysteine, increasing its antidiuretic activity and prolonging its action, and substituting L-arginine with D-arginine, which considerably reduces its affinity for receptors. V1 and its vasopressor effect.
Due to insufficient hormonal secretion, the primary therapeutic use of structural analogs of vasopressin with little vasoconstrictor effect in treating central diabetes insipidus.
The analog used for its antidiuretic effect is desmopressin. Being a polypeptide, desmopressin is poorly absorbed from the digestive tract and partially inactivated by enzymes in the digestive tract.
It is administered by injection, nasal spray, and even orally, but in the latter case, a very high dose is administered to compensate for its low bioavailability.
In addition to its use in diabetes insipidus, desmopressin is used in the treatment of enuresis (children> 5 years), factor VIII defective bleeding (hemophilia A), or von Willebrand factor. It is also used in functional examination to assess the concentrating power of the kidney.
As an anti-hemorrhagic drug, desmopressin can induce fluid retention with dilutional hyponatremia.
Terlipressin, an inactive prodrug progressively converted to lypressin in the body, is not used in treating diabetes insipidus but rather in treating gastrointestinal bleeding due to ruptured esophageal varies due to its vasoconstrictive effect on the portal circulation. Terlipressin can adversely induce a hypertensive peak.
According to recent studies, vasopressin is as effective as adrenaline in treating cardiac arrest and specific shocks with excessive vasodilation. In these indications, it could be used as an alternative to adrenaline.
Vasopressin receptor antagonists
Vasopressin receptor antagonists can reduce vasoconstriction by inhibiting V1 receptors and increase access by inhibiting V2 receptors.
Conivaptan is a non-peptide antagonist of the V1A and V2 vasopressin receptors. The main pharmacological effect of conivaptan is to induce acres (improved excretion of free water) with an increase in plasma sodium concentration.
It is marketed as Vaprisol * and is used for treating hyponatremia of the syndrome of inappropriate antidiuretic hormone secretion.
Generic names of drugs that have V2 vasopressin antagonist effects end with “vaptan.”