Increased Blood Pressure, Aldosterone Activity, and Regional Differences in Renal ENaC Protein During Vasopressin-Escape Short title: MAP, Aldosterone, and ENaC in vasopressin escape by

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 αand γ(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-β-hydroxysteroid dehydrogenase type 2 (11-β-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 αand γ-ENaC (70-kDa band) were significantly increased in the WL group (relative to dDAVP), only in the cortex. βand γ-ENaC (85-kDa band) were significantly increased by dDAVP relative to control, in cortex and medulla. 11-β-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.