title: Altered expression of renal apical plasma membrane Na+ transporters in the early phase of genetic hypertension.
abstract: The present study explores whether the development of hypertension in the Milan strain of rats (MHS) rats is preceded or paralleled by alterations of mRNA and/or protein levels of the major luminal Na+ transporters. MHS rats were studied at 23-25 days after birth; age-matched Milan normotensive (MNS) rats were used as controls. The glomerular filtration rate (GFR), measured by inulin clearance, was higher in MHS than in MNS rats, while the mean blood pressure was not different in the two strains of animals indicating that the MHS rats were still in the prehypertensive state. Type 3 sodium/hydrogen exchanger (NHE3), bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC) and alpha-ENaC mRNA abundances were quantified by competitive PCR. In MHS compared with MNS, mRNA abundance was unchanged for NHE3 in proximal tubules, higher for NKCC2 in medullary thick ascending limbs of Henle's loops (TAL) and lower for NCC in distal convoluted tubules (DCT) and for alpha-ENaC along collecting ducts (CD). Western blot experiments revealed 1) unchanged NHE3; 2) a significant increase in NKCC2 in the outer medulla; 3) a significant decrease in NCC in the renal cortex and of alpha-ENaC in both the renal cortex and outer medulla, whereas beta- and gamma-ENaC remained unchanged. These data indicate that, in MHS rats, there is a strong upregulation of NKCC2 along the TAL associated with increased GFR, robust inhibition of NCC cotransporter along the DCT and modest downregulation of alpha-ENaC along the CD. The interplay of the various Na+ transporters may well explain why, at this age, the rats are still in the prehypertensive state.
authors.affiliation: Nephrology, Second Univ. of Napoli, Nuovo Policlinico, Padiglione 17, Via Pansini 5, 80131 Naples, Italy. gb.capasso@unina2.it
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.forename: Maria
authors.initials: M
authors.lastname: Rizzo
authors.forename: Ciriana
authors.initials: C
authors.lastname: Evangelista
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferrari
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Geelen
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D053503:Epithelial Sodium Channels; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008138:Loop of Henle / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters / Q000235:genetics / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters