Regulation of renal salt and water transporters during vasopressin escape.
Hyponatremia, defined as a serum sodium < 135 mmol/l, is one of the most commonly encountered and serious electrolyte disorders of clinical medicine. The predominant cause of hyponatremia is an inappropriate elevation of circulating vasopressin levels relative to serum osmolality or the 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH). Fortunately, the degree of the hyponatremia is limited by a process that counters the water-retaining action of vasopressin, namely 'vasopressin escape'. Vasopressin escape is characterized by a sudden increase in urine volume with a decrease in urine osmolality independent of circulating vasopressin levels. Until recently, little was known about the molecular mechanisms underlying escape. In the 1980s, we developed an animal model for vasopressin escape in which male Sprague-Dawley rats were infused with dDAVP, a V2-receptor-selective agonist of vasopressin, while being fed a liquid diet. Rats drank a lot of water in order to get the calories they desired. Using this model, we demonstrated that the onset of vasopressin escape (increased urine volume coupled to decreased urine osmolality) coincided temporally with a marked decrease in renal aquaporin-2 (water channel) protein and mRNA expression in renal collecting ducts. This protein reduction was reversible and correlated to decreased water permeability of the collecting duct. Studies examining the mechanisms underlying AQP2 decrease revealed a decrease in V2-receptor mRNA expression and binding, as well as a decrease in cyclic AMP production in response to acute-dDAVP challenge in collecting duct suspensions from these escape animals. Additional studies showed an increase in sodium transporters of the distal tubule. These changes, hypothetically, might help to attenuate the hyponatremia. Future studies are needed to fully elucidate systemic, intra-organ, and cellular signaling responsible for the physiological phenomenon of vasopressin escape.
Ecelbarger
Carolyn A
CA
Department of Medicine, Division of Endocrinology and Metabolism, Building D, Room 232, 4000 Reservoir Road NW, Georgetown University, Washington, DC 20007, USA. ecelbarc@georgetown.edu
Murase
Takashi
T
Tian
Ying
Y
Nielsen
Soren
S
Knepper
Mark A
MA
Verbalis
Joseph G
JG
D000818:Animals; D020346:Aquaporins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004231:Diuresis; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009318:Natriuresis; D051381:Rats; D014667:Vasopressins / Q000502:physiology*; D014883:Water-Electrolyte Imbalance / Q000503:physiopathology*
D020346:Aquaporins; D002352:Carrier Proteins; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin