Pathophysiological roles of arginine vasopressin and aquaporin-2 in impaired water excretion.

Abstract

Impaired water excretion occurs in patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), adrenal insufficiency, congestive heart failure and liver cirrhosis with ascites (Bartter & Schwartz, 1967; Schrier, 1988a,b). In these clinical settings, there is hyponatraemia to various extents. Nonsuppressible release of arginine vasopressin (AVP, ADH) is found despite hypoosmolality, which should suppress AVP release to undetectable levels. Reversal of hyponatraemia by specific antagonists of AVP provides conclusive evidence for the role of AVP in pathological states of water retention. In response to AVP, concentrated urine is produced by water reabsorption across renal collecting ducts (Ishikawa, 1993; Knepper & Rector, 1995). The aquaporin-2 (AQP-2) water channel was discovered by Sasaki and colleagues (Fushimi et al ., 1993), and is an AVP-regulated water channel in collecting duct cells. There are two regulatory systems: short-term and long-term regulation. The upregulation of kidney AQP-2 expression is closely related to the nonsuppressible release of AVP in the experimental models of SIADH, liver cirrhosis, congestive heart failure, and adrenal insufficiency (Asahina et al ., 1995; Fujita et al ., 1995; Nielsen et al ., 1997; Xu et al ., 1997; Saito et al ., 2000). Kidney AQP-2 expression has been quantitatively estimated by urinary excretion of AQP-2 (Kanno et al ., 1995; Rai et al ., 1997). Approximately 3% of AQP-2 in the collecting duct cells is excreted into urine (Rai et al ., 1997), and urinary excretion of AQP-2 positively correlates with plasma AVP levels in normal subjects (Saito et al ., 1997c). In this review, we focus on the close association of kidney AQP-2 expression with exaggerated release of AVP in pathological states of impaired water excretion. Furthermore, the diagnostic value of urinary excretion of AQP-2 in disorders of water metabolism dependent on AVP is discussed. Secretion of arginine vasopressin