Contr. Nephrol., vol. 14, pp. 50-63 (Karger, Basel 1978)
Physiology of Renal Water Excretion Robert J. Anderson and Robert W. Schrier Department of Medicine, University of Colorado Medical Center, Denver, Colo.
Introduction Smith (1) in his description of the evolution of the mammalian kidney, noted that the movement of vertebrates from a salt water to a fresh water environment required the development of mechanisms to protect the organism from fatal dilution. This need to excrete hypotonic fluid was met by the development of a segment of the nephron where electrolyte could be reabsorbed without water, thus resulting in the formation of hypotonic urine. In normal man, this diluting mechanism is a high capacity system enabling excretion of up to 25 l/day while maintaining constancy of body fluid tonicity (2). This chapter will deal with the physiologic considerations involved in the urinary diluting process.
The processes of water excretion and conservation, when closely coupled with mechanisms controlling fluid intake (thirst), allow man to regulate body fluid tonicity at a remarkably constant level. This regulation of tonicity is important because of the freely permeable nature of water across cell membranes and the relative impermeability of sodium across the same membranes. Thus, dilution of extracellular fluid (ECF) and resultant hyponatremia will result in water transfer down its concentration gradient into cells and cell swelling. Conversely, hypernatremia and resultant dehydration of ECF will result in removal of cell water and cellular crenation. Thus, maintenance of isotonicity of ECF is important in protecting the organism from the deleterious effects of alterations in cell volume.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Overview of Body Fluid Tonicity Regulation
Renal Water Excretion
51
The maintenance of tonicity of body fluid is a function of the sensitive (1-2% threshold) osmotic control of thirst and vasopressin secretion. For example, water ingestion results in a small decrease in ECF tonicity. This decrease in tonicity suppresses both thirst and the secretion of vasopressin. Suppression of vasopressin secretion renders the target tissue for vasopressin, namely the collecting duct epithelium, impermeable to water reabsorption. Urinary dilution then results in the excretion of solute-free water, thereby restoring ECF tonicity to normal. Conversely, when water intake is diminished, the small increase in ECF tonicity results in thirst stimulation and vasopressin release. Vasopressin then increases collecting duct water permeability which allows for water reabsorption. This water retention, when coupled with increased water intake, returns ECF tonicity to normal. On the background of this overview of body fluid tonicity regulation, we will now discuss in more detail the renal diluting mechanism.
ReMI Dilution Mechanism
The previously mentioned ability of normal man to ingest large volumes of fluid without fatal dilution is dependent upon the excretion of large volumes of urine more dilute than plasma. The elaboration of dilute urine can best be visualized as occurring in 3 sequential steps (table I, fig. 1): (1) delivery of tubular fluid to the distal diluting site of the nephron (primarily the thick ascending limb of Henle's loop); (2) separation of electrolyte from water at the diluting segment of the nephron, and (3) relative lack of water reabsorption in
Table I. Factors of importance in renal water excretion Delivery of glomerular filtrate to the diluting segment of the nephron A. Glomerular mtration rate B. Proximal tubular fluid reabsorption rate Regulation of water reabsorption at the collecting duct of the nephron A. Factors that regulate vasopressin secretion 1. Osmotic 2. Nonosmotic B. Factors that regulate the action of vasopressin in the collecting duct 1. Cellular factors 2. Hormonal factors 3. Local environmental factors
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Separation of electrolyte from water at the diluting segment of the nephron
52
Anderson/Schrier
..-.:.. .. .. ::. .;t.; ......
@Water impermeability of the collecting duct
mFluid delivery::: 1-+ 1 Electrolytes
1--+ 1
.-
....,.
*. I
Water
Fig. 1. Schematic representation of the 3 components of normal urinary dilution and the nephron sites at which these components are operative.
Delivery of Tubular Fluid to the Distal Nephron Proximal tubular reabsorption of glomerular filtrate is isosmotic in nature. Although this proximal solute and water reabsorption does not dilute the urine, along with glomerular filtration, it determines the volume of filtrate delivered to the more distal diluting segments involved in urine dilution. For example, at a normal glomerular filtration rate (GFR) of 100 ml/min (l44l/day) and at an approximate rate of proximal tubular reabsorption of 80%, 20% of glomerular filtrate (28.8 liters) is delivered out of the proximal tubule to the diluting segment and is ultimately excreted as hypotonic urine provided vasopressin secretion is suppressed. On the other hand, at a GFR of 5 ml/min (7.2l/day) and
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
the collecting duct of the nephron enabling excretion of the solute-free water formed in the diluting segment.
53
a similar rate of proximal fluid reabsorption, only 1.44 liters is delivered to the diluting segment and ultimately excreted. Thus, in the latter circumstance, positive water balance of more than 1.44 liters will result in dilution of ECF. There appear to be at least 3 circumstances in which decreases in delivery of tubular fluid may play a significant role in the failure of normal water excretion. The first circumstance is with renal failure and severe reductions in GFR as demonstrated in the above example. In this regard, experiments performed in dogs without endogenous vasopressin have demonstrated that an acute 50% reduction in GFR can result in the production of hypertonic urine (3). However, from a clinical viewpoint, in patients with severely reduced GFR due to chronic renal failure, the ability to lower urine osmolality to hypotonic levels is retained (4). In these patients, however, the reduction in GFR severely limits both the volume of filtrate that may be delivered to the distal dilution nephron and rate of solute-free water excretion. The second circumstance in which diminished distal delivery of tubular fluid may impair renal water excretion is in the edematous disorders. In these disorders; e.g. heart failure, cirrhosis, and nephrosis, a decreased 'effective' Circulating blood volume may lead to a decrease in GFR and enhanced proximal tubular fluid reabsorption. For example, in patients with heart failure and cirrhosis, maneuvers which expand blood volume and increase distal delivery of tubular fluid result in improved renal water excretion (5, 6). However, these studies do not exclude a role for increased secretion of vasopressin in the impaired water excretion in edematous djsorders, since blood volume expansion also may suppress vasopressin secretion. Furthermore, experimental studies performed in our laboratory in models of acute low output cardiac failure and portal hypertension indicate that, although impaired distal delivery modestly limits water excretion in these models, secretion of vasopressin seems to be the major factor leading to impaired water excretion (7,8). Finally, in the volume-depleted state, in addition to vasopressin release, it is also likely that diminished GFR and decreased distal delivery of tubular fluid plays a role in the impaired water excretion. In this regard, sodium depletion of rats with a congenital absence of vasopressin can cause diminished ability to excrete water and result in hyponatremia in these animals (9). Thus, if GFR is decreased and/or proximal tubular reabsorption is markedly increased, the diminution in quantity of fluid delivered to the distal nephron will limit the rate of renal water excretion even if other components of the diluting mechanism are intact. It is important to emphasize, however, that the primary factor resulting in impaired renal dilution of sufficient magnitude to result in hypoosmolality is generally persistent secretion o(vasopressin (see below). In this regard, substantial diminished delivery of tubular fluid (for example, a 50% reduction in GFR and a 10% increase in rate of proximal tubular fluid reabsorption) still allows for excretion of 5-7 liters of hypotonic fluid. This magnitude
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Renal Water Excretion
Anderson/Schrier
54
of defect resulting from impaired distal delivery of tubular fluid will not result in a hyponatremia at usual levels of fluid intake. Dilution of Tubular Fluid - Transport of Solute without Water in the Ascending Limb of Henle's Loop The excretion of urine hypotonic to plasma requires that electrolyte be reabsorbed in preference to water at some nephron segment. In the mammalian nephron, it is known that the entire ascending limb of Henle's loop is waterimpermeable (10, 11) and has the capacity to actively reabsorb chloride (12). Thus, the active transport of chloride and passive transport of sodium without water leads to generation of hypotonic fluid at the distal end of the thick ascending limb of Henle (~150 mosm/kg H 2 0) (13). A disturbance in the function of the thick ascending limb can thus impair urinary dilution. For example, so-called loop diuretics including furosemide and ethacrynic acid impair active chloride transport in the ascending limb and thus impair urinary dilution. This effect most certainly contributes to the hyponatremia which can occur as a complication of diuretic use. Regulation of Water Permeability of the Collecting Duct by Alterations in Vasopressin Secretion The excretion of urine rendered hypotonic by the ascending limb of Henle's loop requires continued solute reabsorption and relative water impermeability in the terminal portion (collecting ducts) of the nephron. The water permeability of the collecting duct is primarily dependent on the presence or absence of vasopressin (14). Thus, this hormone plays a critical role in determining the fate of fluid delivered to the collecting duct and therefore concentration and dilution of the urine. In the absence of vasopressin, the collecting duct is nearly, but not totally, impermeable to water (15). The continued reabsorption of solute then results in excretion of maximally dilute urine (approximately 50 mosm/kg H 2 0). Since the renal medullary interstitium is always hypertonic, the absence of vasopressin, and thus water impermeability of the collecting duct, is necessary to
Osmolar Nonosmolar A. Effective circulating blood volume 1. Intravascular volume 2. Cardiac output 3. Mean arterial blood pressure B. Emotional and/or physical stress C. Pharmacologic agents D. ? Hormonal agents
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Table II. Factors that control vasopressin secretion
Renal Water Excretion
55
avoid osmotic water movement from the hypotonic tubule lumen to the hypertonic interstitium. Because of the pivotal role of vasopressin in urinary dilution, it is important to examine closely the factors responsible for its secretion (table II). Under normal circumstances, very small alterations in plasma osmolality result in reciprocal changes in vasopressin secretion, thereby affecting urinary dilution and concentration (16). However, for vasopressin secretion to play an important role in the initiation and/or maintenance phase of hypoosmolality syndromes, nonosmotic stimuli for vasopressin secretion must exist which are capable of overriding the influence of hypoosmolality per se to suppress vasopressin secretion (17, 18). As seen in table II, a number of stimuli that result in a diminished 'effective' circulating blood volume are capable of inducing nonosmotic release of vasopressin. Maintenance of normal circulating volume at the expense of abnormal ECF tonicity has been shown by Rydin and Verney (19) in experiments in which the diuresis associated with a decrease in plasma osmolality could be blunted by nonhypotensive hemorrhage. Subsequently, a number of both clinical and experimental studies support a role for a variety of hypovolemic stimuli to provoke vasopressin release and result in impaired urinary dilution in various hypoosmolality syndromes (17, 18). Recent studies from our and other laboratories have clarified the neural pathways whereby alterations in volume are conveyed to the hypothalamus and thereby modulate the nonosmolar secretion of vasopressin (fig. 2). For example,
I JParasympathetic Afferent Pathways
/
1) Beta Adrenergic Stimulus 2) Alpha Adrenergic Stimulus 3) Nicotine
Fig. 2. Factors that induce nonosmotic release of vasopressin through alterations in afferent parasympathetic neural pathways.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
4) , Cardiac Output 5) Atrial Tachycardia 6) Hypoxia
Anderson/Schrier
56
Intact Neurohypophyseal Tract
Hypophysectom ized
ThoracIc
Pre-control
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Vena Cava
ThoracIC InlerlOf 'vena Cava
POSI-conuol
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400
200
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Fig. 3. Effect of acute thoracic inferior vena cava constriction, a model of acute low output cardiac failure, in dogs undergoing a water diuresis. The antidiuresis of this maneuver could be abolished by either removal of the source of vasopressin (middle panel) or by interruption of afferent parasympathetic pathways (third panel).
the diuretic response to atrial distension (20) and atrial tachycardia (21) can be abolished by cervical vagotomy, suggesting these parasympathetic fibers provide the afferent pathway whereby alterations in the low pressure atrial receptor system effect vasopressin release. In addition, receptors capable of modulating vasopressin release also exist in the high-pressure arterial system (22, 23). These baroreceptors are located in the carotid sinus and aortic arch and are activated by volume contraction, particularly when accompanied by decreased cardiac output or arterial pressure . Parasympathetic afferent fibers also link these baroreceptors to the hypothalamus as evidenced by the fact that baroreceptor denervation abolishes alterations in urine flow to both increases and decreases in mean arterial pressure (22) and in cardiac output as demonstrated from a number of studies in our laboratory (fig. 3) (22). Furthermore, other studies from our laboratory demonstrate that additional stimuli to vasopressin secretion such as nicotine administration (24) and hypoxia (25) may also operate via parasympathetic afferent neural pathways. Taken together, it is thus likely that insults which result in a decreased 'effective' circulatory volume can lead to vasopressin secretion via these pathways. In this way, non osmolar secretion of vasopressin is no doubt important in the generation of hypoosmolality in association with volume-contracted states, as well as edematous disorders.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
!GIV
57
Renal Water Excretion
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Physiology of Renal Water Excretion Robert J. Anderson and Robert W. Schrier Department of Medicine, University of Colorado Medical Center, Denver, Colo.
Introduction Smith (1) in his description of the evolution of the mammalian kidney, noted that the movement of vertebrates from a salt water to a fresh water environment required the development of mechanisms to protect the organism from fatal dilution. This need to excrete hypotonic fluid was met by the development of a segment of the nephron where electrolyte could be reabsorbed without water, thus resulting in the formation of hypotonic urine. In normal man, this diluting mechanism is a high capacity system enabling excretion of up to 25 l/day while maintaining constancy of body fluid tonicity (2). This chapter will deal with the physiologic considerations involved in the urinary diluting process.
The processes of water excretion and conservation, when closely coupled with mechanisms controlling fluid intake (thirst), allow man to regulate body fluid tonicity at a remarkably constant level. This regulation of tonicity is important because of the freely permeable nature of water across cell membranes and the relative impermeability of sodium across the same membranes. Thus, dilution of extracellular fluid (ECF) and resultant hyponatremia will result in water transfer down its concentration gradient into cells and cell swelling. Conversely, hypernatremia and resultant dehydration of ECF will result in removal of cell water and cellular crenation. Thus, maintenance of isotonicity of ECF is important in protecting the organism from the deleterious effects of alterations in cell volume.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Overview of Body Fluid Tonicity Regulation
Renal Water Excretion
51
The maintenance of tonicity of body fluid is a function of the sensitive (1-2% threshold) osmotic control of thirst and vasopressin secretion. For example, water ingestion results in a small decrease in ECF tonicity. This decrease in tonicity suppresses both thirst and the secretion of vasopressin. Suppression of vasopressin secretion renders the target tissue for vasopressin, namely the collecting duct epithelium, impermeable to water reabsorption. Urinary dilution then results in the excretion of solute-free water, thereby restoring ECF tonicity to normal. Conversely, when water intake is diminished, the small increase in ECF tonicity results in thirst stimulation and vasopressin release. Vasopressin then increases collecting duct water permeability which allows for water reabsorption. This water retention, when coupled with increased water intake, returns ECF tonicity to normal. On the background of this overview of body fluid tonicity regulation, we will now discuss in more detail the renal diluting mechanism.
ReMI Dilution Mechanism
The previously mentioned ability of normal man to ingest large volumes of fluid without fatal dilution is dependent upon the excretion of large volumes of urine more dilute than plasma. The elaboration of dilute urine can best be visualized as occurring in 3 sequential steps (table I, fig. 1): (1) delivery of tubular fluid to the distal diluting site of the nephron (primarily the thick ascending limb of Henle's loop); (2) separation of electrolyte from water at the diluting segment of the nephron, and (3) relative lack of water reabsorption in
Table I. Factors of importance in renal water excretion Delivery of glomerular filtrate to the diluting segment of the nephron A. Glomerular mtration rate B. Proximal tubular fluid reabsorption rate Regulation of water reabsorption at the collecting duct of the nephron A. Factors that regulate vasopressin secretion 1. Osmotic 2. Nonosmotic B. Factors that regulate the action of vasopressin in the collecting duct 1. Cellular factors 2. Hormonal factors 3. Local environmental factors
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Separation of electrolyte from water at the diluting segment of the nephron
52
Anderson/Schrier
..-.:.. .. .. ::. .;t.; ......
@Water impermeability of the collecting duct
mFluid delivery::: 1-+ 1 Electrolytes
1--+ 1
.-
....,.
*. I
Water
Fig. 1. Schematic representation of the 3 components of normal urinary dilution and the nephron sites at which these components are operative.
Delivery of Tubular Fluid to the Distal Nephron Proximal tubular reabsorption of glomerular filtrate is isosmotic in nature. Although this proximal solute and water reabsorption does not dilute the urine, along with glomerular filtration, it determines the volume of filtrate delivered to the more distal diluting segments involved in urine dilution. For example, at a normal glomerular filtration rate (GFR) of 100 ml/min (l44l/day) and at an approximate rate of proximal tubular reabsorption of 80%, 20% of glomerular filtrate (28.8 liters) is delivered out of the proximal tubule to the diluting segment and is ultimately excreted as hypotonic urine provided vasopressin secretion is suppressed. On the other hand, at a GFR of 5 ml/min (7.2l/day) and
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
the collecting duct of the nephron enabling excretion of the solute-free water formed in the diluting segment.
53
a similar rate of proximal fluid reabsorption, only 1.44 liters is delivered to the diluting segment and ultimately excreted. Thus, in the latter circumstance, positive water balance of more than 1.44 liters will result in dilution of ECF. There appear to be at least 3 circumstances in which decreases in delivery of tubular fluid may play a significant role in the failure of normal water excretion. The first circumstance is with renal failure and severe reductions in GFR as demonstrated in the above example. In this regard, experiments performed in dogs without endogenous vasopressin have demonstrated that an acute 50% reduction in GFR can result in the production of hypertonic urine (3). However, from a clinical viewpoint, in patients with severely reduced GFR due to chronic renal failure, the ability to lower urine osmolality to hypotonic levels is retained (4). In these patients, however, the reduction in GFR severely limits both the volume of filtrate that may be delivered to the distal dilution nephron and rate of solute-free water excretion. The second circumstance in which diminished distal delivery of tubular fluid may impair renal water excretion is in the edematous disorders. In these disorders; e.g. heart failure, cirrhosis, and nephrosis, a decreased 'effective' Circulating blood volume may lead to a decrease in GFR and enhanced proximal tubular fluid reabsorption. For example, in patients with heart failure and cirrhosis, maneuvers which expand blood volume and increase distal delivery of tubular fluid result in improved renal water excretion (5, 6). However, these studies do not exclude a role for increased secretion of vasopressin in the impaired water excretion in edematous djsorders, since blood volume expansion also may suppress vasopressin secretion. Furthermore, experimental studies performed in our laboratory in models of acute low output cardiac failure and portal hypertension indicate that, although impaired distal delivery modestly limits water excretion in these models, secretion of vasopressin seems to be the major factor leading to impaired water excretion (7,8). Finally, in the volume-depleted state, in addition to vasopressin release, it is also likely that diminished GFR and decreased distal delivery of tubular fluid plays a role in the impaired water excretion. In this regard, sodium depletion of rats with a congenital absence of vasopressin can cause diminished ability to excrete water and result in hyponatremia in these animals (9). Thus, if GFR is decreased and/or proximal tubular reabsorption is markedly increased, the diminution in quantity of fluid delivered to the distal nephron will limit the rate of renal water excretion even if other components of the diluting mechanism are intact. It is important to emphasize, however, that the primary factor resulting in impaired renal dilution of sufficient magnitude to result in hypoosmolality is generally persistent secretion o(vasopressin (see below). In this regard, substantial diminished delivery of tubular fluid (for example, a 50% reduction in GFR and a 10% increase in rate of proximal tubular fluid reabsorption) still allows for excretion of 5-7 liters of hypotonic fluid. This magnitude
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Renal Water Excretion
Anderson/Schrier
54
of defect resulting from impaired distal delivery of tubular fluid will not result in a hyponatremia at usual levels of fluid intake. Dilution of Tubular Fluid - Transport of Solute without Water in the Ascending Limb of Henle's Loop The excretion of urine hypotonic to plasma requires that electrolyte be reabsorbed in preference to water at some nephron segment. In the mammalian nephron, it is known that the entire ascending limb of Henle's loop is waterimpermeable (10, 11) and has the capacity to actively reabsorb chloride (12). Thus, the active transport of chloride and passive transport of sodium without water leads to generation of hypotonic fluid at the distal end of the thick ascending limb of Henle (~150 mosm/kg H 2 0) (13). A disturbance in the function of the thick ascending limb can thus impair urinary dilution. For example, so-called loop diuretics including furosemide and ethacrynic acid impair active chloride transport in the ascending limb and thus impair urinary dilution. This effect most certainly contributes to the hyponatremia which can occur as a complication of diuretic use. Regulation of Water Permeability of the Collecting Duct by Alterations in Vasopressin Secretion The excretion of urine rendered hypotonic by the ascending limb of Henle's loop requires continued solute reabsorption and relative water impermeability in the terminal portion (collecting ducts) of the nephron. The water permeability of the collecting duct is primarily dependent on the presence or absence of vasopressin (14). Thus, this hormone plays a critical role in determining the fate of fluid delivered to the collecting duct and therefore concentration and dilution of the urine. In the absence of vasopressin, the collecting duct is nearly, but not totally, impermeable to water (15). The continued reabsorption of solute then results in excretion of maximally dilute urine (approximately 50 mosm/kg H 2 0). Since the renal medullary interstitium is always hypertonic, the absence of vasopressin, and thus water impermeability of the collecting duct, is necessary to
Osmolar Nonosmolar A. Effective circulating blood volume 1. Intravascular volume 2. Cardiac output 3. Mean arterial blood pressure B. Emotional and/or physical stress C. Pharmacologic agents D. ? Hormonal agents
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
Table II. Factors that control vasopressin secretion
Renal Water Excretion
55
avoid osmotic water movement from the hypotonic tubule lumen to the hypertonic interstitium. Because of the pivotal role of vasopressin in urinary dilution, it is important to examine closely the factors responsible for its secretion (table II). Under normal circumstances, very small alterations in plasma osmolality result in reciprocal changes in vasopressin secretion, thereby affecting urinary dilution and concentration (16). However, for vasopressin secretion to play an important role in the initiation and/or maintenance phase of hypoosmolality syndromes, nonosmotic stimuli for vasopressin secretion must exist which are capable of overriding the influence of hypoosmolality per se to suppress vasopressin secretion (17, 18). As seen in table II, a number of stimuli that result in a diminished 'effective' circulating blood volume are capable of inducing nonosmotic release of vasopressin. Maintenance of normal circulating volume at the expense of abnormal ECF tonicity has been shown by Rydin and Verney (19) in experiments in which the diuresis associated with a decrease in plasma osmolality could be blunted by nonhypotensive hemorrhage. Subsequently, a number of both clinical and experimental studies support a role for a variety of hypovolemic stimuli to provoke vasopressin release and result in impaired urinary dilution in various hypoosmolality syndromes (17, 18). Recent studies from our and other laboratories have clarified the neural pathways whereby alterations in volume are conveyed to the hypothalamus and thereby modulate the nonosmolar secretion of vasopressin (fig. 2). For example,
I JParasympathetic Afferent Pathways
/
1) Beta Adrenergic Stimulus 2) Alpha Adrenergic Stimulus 3) Nicotine
Fig. 2. Factors that induce nonosmotic release of vasopressin through alterations in afferent parasympathetic neural pathways.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
4) , Cardiac Output 5) Atrial Tachycardia 6) Hypoxia
Anderson/Schrier
56
Intact Neurohypophyseal Tract
Hypophysectom ized
ThoracIc
Pre-control
InlerlOf
Vena Cava
ThoracIC InlerlOf 'vena Cava
POSI-conuol
ConstrICtion
Post ""Control
Denervated Baroreceptors P,e-eontroi
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ConstrICtIOn
ConS\tlCtlOn
1000
..
o
?;N
?: -= :t ~
600
coO> '::E~
~
\I)
E o
0",
..s
400
200
40
! 8e .. c 3 e.§ 20
:e
0
~-
::::- ---
~
- -~~:.."..- -
Fig. 3. Effect of acute thoracic inferior vena cava constriction, a model of acute low output cardiac failure, in dogs undergoing a water diuresis. The antidiuresis of this maneuver could be abolished by either removal of the source of vasopressin (middle panel) or by interruption of afferent parasympathetic pathways (third panel).
the diuretic response to atrial distension (20) and atrial tachycardia (21) can be abolished by cervical vagotomy, suggesting these parasympathetic fibers provide the afferent pathway whereby alterations in the low pressure atrial receptor system effect vasopressin release. In addition, receptors capable of modulating vasopressin release also exist in the high-pressure arterial system (22, 23). These baroreceptors are located in the carotid sinus and aortic arch and are activated by volume contraction, particularly when accompanied by decreased cardiac output or arterial pressure . Parasympathetic afferent fibers also link these baroreceptors to the hypothalamus as evidenced by the fact that baroreceptor denervation abolishes alterations in urine flow to both increases and decreases in mean arterial pressure (22) and in cardiac output as demonstrated from a number of studies in our laboratory (fig. 3) (22). Furthermore, other studies from our laboratory demonstrate that additional stimuli to vasopressin secretion such as nicotine administration (24) and hypoxia (25) may also operate via parasympathetic afferent neural pathways. Taken together, it is thus likely that insults which result in a decreased 'effective' circulatory volume can lead to vasopressin secretion via these pathways. In this way, non osmolar secretion of vasopressin is no doubt important in the generation of hypoosmolality in association with volume-contracted states, as well as edematous disorders.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/1/2017 12:33:30 PM
!GIV
57
Renal Water Excretion
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