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OBJECTIVES
After reading this chapter, you should be able to:
Describe how the tonicity (osmolality) of the extracellular fluid is maintained by alterations in water intake and vasopressin secretion.
Discuss the effects of vasopressin, the receptors on which it acts, and how its secretion is regulated.
Describe how the volume of the extracellular fluid is maintained by alterations in renin and aldosterone secretion.
Outline the cascade of reactions that lead to the formation of angiotensin II and its metabolites in the circulation.
List the functions of angiotensin II and the receptors on which it acts to carry out these functions.
Describe the structure and functions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and the receptors on which they act.
Describe the site and mechanism of action of erythropoietin, and the feedback regulation of its secretion.
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VASOPRESSIN AND DEFENSE OF TONICITY
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The defense of the tonicity of the extracellular fluid (ECF) is primarily the function of the vasopressin-secreting and thirst mechanisms. The total body osmolality is directly proportional to the total body sodium plus the total body potassium divided by the total body water, so that changes in the osmolality of the body fluids occur when a mismatch exists between the amount of these electrolytes and the amount of water ingested or lost from the body. 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. 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 mOsm/kg of H2O to 295 mOsm/kg of H2O, with vasopressin secretion maximally inhibited at 285 mOsm/kg and stimulated at higher values.
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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. The half-life of vasopressin is 18 min.
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Vasopressin is often called the antidiuretic hormone (ADH) since it acts on the kidney to reduce water excretion by increasing collecting duct permeability. The urine becomes concentrated, and volume decreases, and body fluid osmolality decreases. In the absence of vasopressin, urine is hypotonic to plasma, excreted volume is increased, and there is a net water loss. Consequently, the osmolality of the body fluid rises.
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The mechanism by which vasopressin exerts its antidiuretic effect is activated by V2 receptors and involves aquaporin-2 in the apical (luminal) membranes of ...