PHYSIOLOGICAL REGULATION OF ADH SECRETION



Variations in secretion of ADH by the posterior pituitary occur primarily in response to changes in body osmolality. Normally, osmolality aver­ages approximately 285 mOsm/kg body water. An increase in body osmolality as small as 1 per cent (3 mOsm/kg), such as occurs after 10 to 12 hours of water deprivation, will normally increase ADH secretion (Fig. 67-3). Conversely, reduction in os­molality following administration of an oral water load causes dilution of body fluids and a prompt suppression of ADH secretion. Concomitant stim­ulation and suppression of the hypothalamic thirst center in response to hypertonicity and hy-potonicity, respectively, provides a parallel phys­iological mechanism for regulating body osmo­lality.

In addition to osmotic regulation, several non-osmotic factors (Table 67-4) can influence ADH secretion. Most notable among these is the state of the so-called effective extracellular fluid (ECF) volume, perceived by high-pressure baroreceptors in the aorta and by low-pressure volume receptors in the left atrium. Hypotension and/or decreased effective ECF volume result in stimulation of ADH The relationship of plasma arginine va­sopressin (AVP) to plasma osmolality in normal subjects and patients with various polyuric states. (From Rob­ertson GL, Mahr EA, Athar S, and Sinha T: Development and clinical application of a new method for the ra­dioimmunoassay of arginine vasopressin in human plasma. J Clin Invest 52:2340,1973.)

secretion via adrenergically mediated signals to the hypothalamus. Although minute-by-minute regulation of ADH secretion is probably through its osmotic control mechanism, nonosmotic fac­tors will predominate in situations in which there is diversion of the two stimuli (e.g., hypovolemia in a hypotonic individual).

The principal site of action of ADH is the distal nephron, where the hormone induces an increase in osmotic water permeability of the collecting tubule and collecting duct. Permeability to urea is also increased in response to ADH. The hormone acts through a classic cyclic AMP-depen-dent mechanism that is initiated by binding to a receptor on the basolateral surface of the target cell. This process is modulated by a number of factors, including calcium, prostaglandins, adre­nal corticosteroids, and a variety of adrenergic agents.