The physiology of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders.

Osmotic control for vasopressin release has been recognized for several years. Further understanding of factors affecting the sensitivity and threshold of ADH release has been advanced by the technological development of a sensitive radioimmunoassay. Evidence suggesting that ADH secretion is also mediated by nonosmotic stimuli involving a separate anatomic pathway from the hypothalamic osmoreceptor has been well documented. Experimental results suggest that the parasympathetic afferent pathways from both "high" and "low" pressure receptors constitute the most important nonosmotic pathways for ADH release. Factors such as hypoxia, altered hemodynamic states, alpha- and beta-adrenergic stimuli, nicotine, adrenal insufficiency, and advanced hypothyroidism are likely examples which activate this nonosmotic pathway. Clarification of the exact interrelationship between the osmotic and nonosmotic release of ADH needs further examination, particularly in the area of central neurotransmitters. However, available information allows for the proposal of a model of this interaction and its clinical implications which may explain many cases of "reset osmostat." Recent available data also provide support for ADH playing a role in the maintenance of blood pressure under certain circumstances. Like other potent vasoconstrictors, preliminary evidence suggests that ADH requires transcellular calcium influx for its vascular effects. Adrenal, thyroid, and edematous disorders have all been shown to be associated with abnormal water excretion. The results of recent studies indicate that these abnormal physiological states have impaired water excretion as a result of both nonosmolar factors stimulating ADH release and intrarenal factors, including diminished glomerular filtration rate or increased proximal tubule reabsorption which lead to decreased distal fluid delivery to the diluting segment of the nephron. Verney's original studies demonstrating the osmoreceptor regulation of ADH release remain a milestone in renal physiology. In the past decade, considerable new information about nonosmotic regulation of ADH has led to further understanding of renal water regulation in health and disease; nevertheless, many of these answers have only stimulated the imagination to ponder even more questions.