title: Increased blood pressure, aldosterone activity, and regional differences in renal ENaC protein during vasopressin escape.
abstract: 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 alpha- and gamma (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 11beta-hydroxysteroid dehydrogenase type 2 (11beta-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 V(2) 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 alpha- and gamma-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. Beta- and gamma-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11beta-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.
authors.affiliation: Dept. of Medicine, Georgetown University, Box 571412, Washington, DC 20057-1412, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Xinqun
authors.initials: X
authors.lastname: Hu
authors.forename: Osman
authors.initials: O
authors.lastname: Khan
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Ecelbarger
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015153:Blotting, Western; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000097:blood / Q000652:urine; D053503:Epithelial Sodium Channels; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007177:Inappropriate ADH Syndrome / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism* / Q000502:physiology
chemical_list: D004573:Electrolytes; D053503:Epithelial Sodium Channels; D012076:Renal Agents; D015222:Sodium Channels; D014667:Vasopressins; D000450:Aldosterone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003894:Deamino Arginine Vasopressin