Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape.
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."
Tiwari
Swasti
S
Department of Medicine, and Center for Sex Differences, Bldg D, Rm 232, Georgetown University, 4000 Reservoir Rd NW, Washington, DC 20057-1412, USA.
Packer
Randall K
RK
Hu
Xinqun
X
Sugimura
Yoshihisa
Y
Verbalis
Joseph G
JG
Ecelbarger
Carolyn A
CA
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*
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