title: Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape.
abstract: Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-beta-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."
authors.affiliation: Department of Medicine, and Center for Sex Differences, Bldg D, Rm 232, Georgetown University, 4000 Reservoir Rd NW, Washington, DC 20057-1412, USA.
authors.forename: Swasti
authors.initials: S
authors.lastname: Tiwari
authors.forename: Randall K
authors.initials: RK
authors.lastname: Packer
authors.forename: Xinqun
authors.initials: X
authors.lastname: Hu
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
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 / Q000502:physiology; D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood / Q000502:physiology* / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D003345:Corticosterone / Q000097:blood / Q000502:physiology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000502:physiology; D006929:Hyperaldosteronism / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000503:physiopathology / Q000601:surgery; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000378:metabolism*; D014667:Vasopressins / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D014667:Vasopressins; D000450:Aldosterone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003894:Deamino Arginine Vasopressin; D003345:Corticosterone