Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung.
Vasopressin is known to acutely stimulate sodium transport in the renal collecting duct. We investigated the long-term regulation by vasopressin of the epithelial sodium channel (ENaC) in the rat kidney. Five-day infusion of dDAVP (a V(2) receptor agonist) to Brattleboro rats lacking vasopressin induced a marked increase in beta- and gamma-subunit ENaC mRNA levels in the renal cortex (beta, 85%; gamma, 100%), with no change in alpha-ENaC mRNA. Expression of beta- and gamma-ENaC mRNAs was also enhanced in lung (beta, 49%; gamma, 33%) but not in distal colon (an organ devoid of V(2) receptors). Similar results were obtained in Sprague Dawley rats after either partial water restriction or dDAVP infusion for 5 days. Transepithelial voltage and transepithelial sodium and water net fluxes were measured in isolated perfused cortical collecting ducts of Brattleboro rats. Acute addition of 2x10(-10) mol/L dDAVP to the bath increased sodium and water fluxes in the same proportion, and to a far greater extent in dDAVP-infused than in control Brattleboro rats (change in Na(+) net flux, 337+/-30 versus 49+/-11 pmol. min(-1). mm(-1), respectively; P<0.001). These effects were abolished by amiloride. Extrarenal water losses, partly originating from the lung, were reduced by high plasma vasopressin level. This study shows that vasopressin increases sodium transport in the renal collecting duct and probably in the lung, through a differential transcriptional regulation of ENaC subunits. This effect is followed by isoosmotic water reabsorption and likely contributes to the process of water conservation. It could lead to less efficient sodium excretion, however, and thus participate in some forms of salt-sensitive hypertension.
Nicco
C
C
INSERM Unité 367, Institut du Fer à Moulin, Paris, France.
Wittner
M
M
DiStefano
A
A
Jounier
S
S
Bankir
L
L
Bouby
N
N
D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D053503:Epithelial Sodium Channels; D017136:Ion Transport / Q000187:drug effects; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation; D014882:Water-Electrolyte Balance
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D012076:Renal Agents; D015222:Sodium Channels; D012964:Sodium; D003894:Deamino Arginine Vasopressin