AVP secretion is stimulated by a decrease in blood volume or pressure. The receptors responsible for this response are found in both the low-pressure (left atrium and large pulmonary vessels) and high-pressure (aortic arch and carotid sinus) sides of the circulatory system. These low-pressure receptors can be considered as responding to overall vascular volume since they are located in the high-compliance venous side of the circulatory system where most of the blood is present. The high-pressure receptors, on the other hand, respond to arterial pressure. Both groups of receptors are called baroreceptors and are sensitive to stretch in the respective structures they are located in (e.g., cardiac atrial and aortic arch). Signals from these receptors travel through the vagus and glossopharyngeal nerves to the brainstem (solitary tract nucleus of the medulla oblongata) which is part of the center that relays signals to the AVP secretory cells of the supraoptic and paraventricular hypothalamic nuclei. The baroreceptor system has a lower sensitivity compared to osmoreceptors and requires a 5% to 10% decrease in blood volume or pressure to stimulate AVP secretion. Bradykinin and histamine, which lower pressure, stimulate AVP secretion, while norepinephrine, which increases blood pressure, inhibits AVP secretion. Changes in blood volume and pressure also influence the response to changes in body fluid osmolality. A decrease in blood volume or pressure shifts the set point to lower osmolality values and steepens the relationship, causing the kidneys to continue conserving water even at the expense of reducing body fluid osmolality. An increase in blood volume or pressure has the opposite effect, shifting the set point to higher osmolality values and decreasing the slope. AVP primarily enhances water absorption from tubular fluid in the kidneys. Inadequate release of AVP from the posterior pituitary leads to the excretion of a large volume of dilute urine (polyuria). To compensate for this water loss, individuals with inadequate AVP release must consume a large volume of water (polydipsia) to maintain constant body fluid osmolality. Central diabetes insipidus, also known as pituitary diabetes insipidus, can occur due to inadequate AVP release. It can be inherited but is more commonly caused by head trauma, brain neoplasms, or infections. Individuals with central diabetes insipidus have a defect in urine concentration that can be corrected by administering exogenous AVP. The inherited form of central diabetes insipidus is autosomal dominant and is caused by various mutations in the AVP gene (AVP, copeptin, and neurophysin). Vasopressinase, a cysteine aminopeptidase produced by the human placenta, degrades AVP and can lead to diabetes insipidus in some women. The associated polyuria can be treated with the synthetic AVP analogue desmopressin (DDAVP).
A decrease in blood volume or pressure also stimulates AVP secretion. The receptors responsible for this response are located in both the low-pressure (left atrium and large pulmonary vessels) and the high-pressure (aortic arch and carotid sinus) sides of the circulatory system. Because the low-pressure receptors are located in the high-compliance side of the circulatory system (i.e., venous), and because the majority of blood is in the venous side of the circulatory system, these low-pressure receptors can be viewed as responding to overall vascular volume. The high-pressure receptors respond to arterial pressure. Both groups of receptors are sensitive to stretch of the wall of the structure in which they are located (e.g., cardiac atrial and aortic arch) and are termed baroreceptors. Signals from these receptors are carried in afferent fibers of the vagus and glossopharyngeal nerves to the brainstem (solitary tract nucleus of the medulla oblongata), which is part of the center that ). Signals are then relayed from the brainstem to the
AVP secretory cells of the supraoptic and paraventricular hypothalamic nuclei. The sensitivity of the baroreceptor system is less than that of the osmoreceptors, and a 5% to 10% decrease in blood volume or pressure is required before AVP secretion is stimulated. This is illustrated in
Fig.
35.4B . A number of substances have been shown to alter the secretion of AVP through their effects on blood pressure. These include bradykinin and histamine, which lower pressure and thus stimulate AVP secretion, and norepinephrine, which increases blood pressure and inhibits AVP secretion.
Alterations in blood volume and pressure also affect the response to changes in body fluid osmolality (see
Fig.
35.4C ). With a decrease in blood volume or pressure, the set point is shifted to lower osmolality values and the slope of the relationship is steeper. In terms of survival of the individual this means that faced with circulatory collapse, the kidneys will continue to conserve water, even though by doing so they reduce the osmolality of the body fluids. With an increase in blood volume or pressure, the opposite occurs. The set point is shifted to higher osmolality values and the slope is decreased.
AVP Actions on the Kidneys
The primary action of AVP on the kidneys is to enhance absorption of water from the tubular fluid by increasing • Fig. 35.4 Osmotic and hemodynamic (nonosmotic) control of AVP secretion. A, Effect of changes in plasma osmolality (constant blood volume and pressure) on plasma AVP levels. B, Effect of changes in blood volume or pressure (constant plasma osmolality) on plasma AVP levels. C, Interactions between osmolar and blood volume and pressure stimuli on plasma AVP levels.
Inadequate release of AVP from the posterior pituitary results in excretion of a large volume of dilute urine (polyuria). To compensate for this loss of water the individual must ingest a large volume of water (polydipsia) to maintain constant body fluid osmolality. If the individual is deprived of water, body fluids will become hyperosmotic. This condition is called central diabetes insipidus or pituitary diabetes insipidus. Central diabetes insipidus can be inherited, although this is rare. It occurs more commonly after head trauma and with brain neoplasms or infections. Individuals with central diabetes insipidus have a urine-concentrating defect that can be corrected by administration of exogenous AVP. The inherited (autosomal dominant) form of central diabetes insipidus is due to numerous mutations in all regions of the AVP gene (i.e., AVP, copeptin and neurophysin). The human placenta produces a cysteine aminopeptidase that degrades AVP. In some women the levels of this vasopressinase result in diabetes insipidus. The associated polyuria can be treated by administration of the synthetic AVP analogue desmopressin (DDAVP).