Antidiuretic Hormone

Introduction

Antidiuretic hormone (ADH), also known as vasopressin or arginine vasopressin (AVP), is a peptide hormone that plays a crucial role in regulating the body's retention of water. It is synthesized in the hypothalamus and stored in the posterior pituitary gland. ADH acts primarily on the kidneys to promote water reabsorption, thereby concentrating the urine and reducing urine volume. This hormone is vital for maintaining fluid balance, blood pressure, and overall homeostasis.

Synthesis and Secretion

ADH is synthesized in the hypothalamus, specifically in the supraoptic and paraventricular nuclei. Once synthesized, it is transported down the axons of the hypothalamic-neurohypophyseal tract to the posterior pituitary gland, where it is stored in vesicles. The release of ADH into the bloodstream is triggered by various physiological stimuli, including increased plasma osmolality, decreased blood volume, and low blood pressure.

Mechanism of Action

Upon release, ADH binds to V2 receptors located on the basolateral membrane of the principal cells in the collecting ducts of the kidneys. This binding activates adenylate cyclase, leading to an increase in cyclic AMP (cAMP) levels. The rise in cAMP activates protein kinase A (PKA), which subsequently phosphorylates aquaporin-2 (AQP2) water channels. These phosphorylated AQP2 channels are then inserted into the apical membrane of the collecting duct cells, increasing water permeability and promoting water reabsorption.

Physiological Effects

ADH exerts several physiological effects, including:

Water Reabsorption

The primary effect of ADH is to increase water reabsorption in the kidneys. By inserting AQP2 channels into the apical membrane of collecting duct cells, ADH allows water to be reabsorbed from the tubular fluid back into the bloodstream, thereby concentrating the urine and reducing urine output.

Vasoconstriction

ADH also has vasoconstrictive properties, mediated through V1 receptors located on vascular smooth muscle cells. Binding to V1 receptors activates phospholipase C, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers increase intracellular calcium levels, causing vasoconstriction and an increase in blood pressure.

Regulation of Blood Pressure

By promoting water reabsorption and vasoconstriction, ADH plays a critical role in the regulation of blood pressure. In conditions of hypovolemia or hypotension, ADH release is stimulated to conserve water and maintain blood pressure.

Regulation of ADH Secretion

The secretion of ADH is tightly regulated by several factors:

Osmoreceptors

Osmoreceptors located in the hypothalamus detect changes in plasma osmolality. An increase in plasma osmolality, such as during dehydration, stimulates the release of ADH to promote water reabsorption and restore osmotic balance.

Baroreceptors

Baroreceptors in the carotid sinus and aortic arch sense changes in blood volume and pressure. A decrease in blood volume or pressure triggers ADH release to conserve water and maintain blood pressure.

Other Factors

Various other factors can influence ADH secretion, including stress, pain, nausea, and certain drugs. For example, nicotine and morphine stimulate ADH release, while alcohol inhibits it.

Pathophysiology

Abnormalities in ADH secretion or action can lead to several clinical conditions:

Diabetes Insipidus

Diabetes insipidus (DI) is characterized by excessive urination and thirst due to a deficiency in ADH (central DI) or a resistance to its action (nephrogenic DI). Central DI results from damage to the hypothalamus or pituitary gland, while nephrogenic DI is often due to mutations in the V2 receptor or AQP2 channels.

Syndrome of Inappropriate ADH Secretion (SIADH)

SIADH is a condition characterized by excessive release of ADH, leading to water retention, hyponatremia, and concentrated urine. It can be caused by various factors, including tumors, central nervous system disorders, and certain medications.

Clinical Applications

ADH and its analogs have several clinical applications:

Desmopressin

Desmopressin is a synthetic analog of ADH used to treat central diabetes insipidus, nocturnal enuresis, and certain bleeding disorders. It has a longer half-life and greater selectivity for V2 receptors compared to natural ADH.

Vasopressin Infusion

Vasopressin infusion is used in the management of vasodilatory shock, such as septic shock, to increase blood pressure through its vasoconstrictive effects.

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