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Increased blood pressure, aldosterone activity, and regional differences in renal ENaC protein during vasopressin escape

Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington, District of Columbia 20057

Submitted 9 March 2004 ; accepted in final form 23 June 2004

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the - and (70-kDa-band)-subunits of the epithelial Na⁺ channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated (n = 6) or infused with desmopressin (dDAVP; n = 12, a V₂ receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5–7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and - and -ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. - and -ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na⁺ losses and ameliorate hyponatremia in vasopressin escape.

hyponatremia; syndrome of inappropriate antidiuretic hormone; pressure-natriuresis; renin; 11-hydroxysteroid dehydrogenase; epithelial sodium channel; mean arterial pressure

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