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Am J Physiol Renal Physiol (June 29, 2004). doi:10.1152/ajprenal.00075.2004
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Submitted on March 9, 2004
Accepted on June 23, 2004

Increased Blood Pressure, Aldosterone Activity, and Regional Differences in Renal ENaC Protein During Vasopressin-Escape

Jian Song1, Xinqun Hu1, Osman Khan1, Ying Tian1, Joseph G. Verbalis1, and Carolyn A. Ecelbarger1*

1 Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC, USA

* To whom correspondence should be addressed. E-mail: ecelbarc{at}georgetown.edu.

The syndrome of inappropriate anti-diuretic 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 {alpha}- and {gamma}- (70-kDa band) subunits of the epithelial sodium channel (ENaC) and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure (MAP) via radiotelemetry, aldosterone activity, and cortical versus medullary ENaC subunit and 11-{beta}-hydroxysteroid dehydrogenase type 2 (11-{beta}-HSD-2) protein abundances in escape. Eighteen male, Sprague-Dawley rats (300 g) were sham operated (n = 6) or infused with dDAVP (n = 12, a V2-receptor selective analogue of AVP). After 4 days, 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 versus 104 mm Hg, p <0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1658% of the dDAVP group, respectively. NCC and {alpha}- and {gamma}-ENaC (70-kDa band) were significantly increased in the WL group (relative to dDAVP), only in the cortex. {beta}- and {gamma}-ENaC (85-kDa band) were significantly increased by dDAVP relative to control, in cortex and medulla. 11-{beta}-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate sodium losses and ameliorate hyponatremia in vasopressin escape.




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