ADH or Vasopression
Because one of its principal physiologic effects is the retention of water by the kidney, vasopressin is often called the antidiuretic hormone ( ADH). It increases the permeability of the collecting ducts of the kidney, so that water enters the hypertonic interstitium of the renal pyramids. The urine becomes concentrated, and its volume decreases. The overall effect is therefore retention of water in excess of solute; consequently, the effective osmotic pressure of the body fluids is decreased. In the absence of vasopressin, the urine is hypotonic to plasma, urine volume is increased, and there is a net water loss. Consequently, the osmolality of the body fluid rises.
The mechanism by which vasopressin exerts its antidiuretic effect is activated by V2 receptors and involves the insertion of aquaporin 2 into the apical (luminal) membranes of the principal cells of the collecting ducts. Movement of water across membranes by simple diffusion is now known to be augmented by movement through these water channels. These channels are stored in endosomes inside the cells, and vasopressin causes their rapid translocation to the luminal membranes.
V1A receptors mediate the vasoconstrictor effect of vasopressin, and vasopressin is a potent stimulator of vascular smooth muscle in vitro. However, relatively large amounts of vasopressin are needed to raise blood pressure in vivo, because vasopressin also acts on the brain to decrease in cardiac output. The site of this action is the area postrema, one of the circumventricular organs. Hemorrhage is a potent stimulus for vasopressin secretion, and the blood pressure fall after hemorrhage is more marked in animals that have been treated with synthetic peptides that block the pressor action of vasopressin. Consequently, it appears that vasopressin does play a role in blood pressure homeostasis.
V1A receptors are also found in the liver and the brain. Vasopressin causes glycogenolysis in the liver, and, as noted above, it is a neurotransmitter in the brain and spinal cord.
The V1B receptors (also called V3 receptors) appear to be unique to the anterior pituitary, where they mediate increased secretion of adrenocorticotropic hormone ( ACTH) from the corticotropes.
Metabolism
Circulating vasopressin is rapidly inactivated, principally in the liver and kidneys. It has a biologic half-life of approximately 18 min in humans.
When the effective osmotic pressure of the plasma rises, vasopressin secretion is increased and the thirst mechanism is stimulated; water is retained in the body, diluting the hypertonic plasma; and water intake is increased (See Figure Below).
Mechanisms for defending ECF tonicity. The dashed arrow indicates inhibition
Conversely, when the plasma becomes hypotonic, vasopressin secretion is decreased and “solute-free water” (water in excess of solute) is excreted. In this way, the tonicity of the body fluids is maintained within a narrow normal range. In health, plasma osmolality ranges from 280 to 295 mOsm/kg of H2O, with vasopressin secretion maximally inhibited at 285 mOsm/kg and stimulated at higher values (See Figure Below).
Relation between plasma osmolality and plasma vasopressin in healthy adult humans during infusion of hypertonic saline. LD, limit of detection. (Reproduced with permission from Thompson CJ, et al: The osmotic thresholds for thirst and vasopressin are similar in healthy humans. Clin Sci [Colch] 1986;71:651.)
Vasopressin is stored in the posterior pituitary and released into the bloodstream in response to impulses in the nerve fibers that contain the hormone. The factors affecting its secretion are summarized in Table 38–1. When the effective osmotic pressure of the plasma is increased above 285 mOsm/kg, the rate of discharge of neurons containing vasopressin increases and vasopressin secretion occurs (Figure 38–2). At 285 mOsm/kg, plasma vasopressin is at or near the limits of detection by available assays, but its levels probably decrease when plasma osmolality is below this level. Vasopressin secretion is regulated by osmoreceptors located in the anterior hypothalamus. They are outside the blood–brain barrier and appear to be located in the circumventricular organs, primarily the organum vasculosum of the lamina terminalis (OVLT) (see Chapter 33). The osmotic threshold for thirst (Figure 38–1) is the same as or slightly greater than the threshold for increased vasopressin secretion (Figure 38–2), and it is still uncertain whether the same osmoreceptors mediate both effects.
Summary of Stimuli Affecting Vasopressin Secretion.
| Vasopressin Secretion Increased | Vasopressin Secretion Decreased |
|---|---|
| Increased effective osmotic pressure of plasma | Decreased effective osmotic pressure of plasma |
| Decreased ECF volume | Increased ECF volume |
| Pain, emotion, “stress,” exercise | Alcohol |
| Nausea and vomiting | |
| Standing | |
| Clofibrate, carbamazepine | |
| Angiotensin II |
Vasopressin secretion is thus controlled by a delicate feedback mechanism that operates continuously to defend the osmolality of the plasma. Significant changes in secretion occur when osmolality is changed as little as 1%. In this way, the osmolality of the plasma in normal individuals is maintained very close to 285 mOsm/L.
Volume Effects on Vasopressin Secretion
ECF volume also affects vasopressin secretion. Vasopressin secretion is increased when ECF volume is low and decreased when ECF volume is high (Table 38–1). There is an inverse relationship between the rate of vasopressin secretion and the rate of discharge in afferents from stretch receptors in the low- and high-pressure portions of the vascular system. The low-pressure receptors are those in the great veins, right and left atria, and pulmonary vessels; the high-pressure receptors are those in the carotid sinuses and aortic arch (see Chapter 32). The exponential increases in plasma vasopressin produced by decreases in blood pressure are documented in Figure 38–3. However, the low-pressure receptors monitor the fullness of the vascular system, and moderate decreases in blood volume that reduce central venous pressure without lowering arterial pressure can also increase plasma vasopressin.
Vasopressin Receptors
There are at least three kinds of vasopressin receptors: V1A, V1B, and V2. All are G protein-coupled. The V1A and V1B receptors act through phosphatidylinositol hydrolysis to increase the intracellular Ca2+ concentration. The V2 receptors act through Gs to increase cyclic adenosine 3',5'-monophosphate (cAMP) levels.
Vasopressin, active in the regulation of total body water, differs from oxytocin by only two amino acids and is also released from the posterior pituitary gland.
Oxytocin
Oxytocin is mainly synthesized by the paraventricular nuclei
Oxytocin causes contraction of the uterus,
Oxytocin is a nine-amino-acid peptide, including a disulfide bridge formed by two cysteine residues.
The anatomic structure of the posterior pituitary becomes important in head trauma, where the axons in the pituitary stalk (infundibulum) can become disrupted, causing central diabetes insipidus from the loss of ADH secretion.
A 32-year-old women complains of amenorrhea since delivery of a baby 15 months previously, despite the fact that she did not breastfeed her baby. The delivery was complicated by excessive hemorrhage that required transfusion of 2.5 liters of blood. She has also been fatigued and has gained an additional 10 pounds (4.5 kg) since the baby was born. Laboratory data is likely to show the following: