HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F556    most recent 00340.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Capasso, G. Articles by Meyer, G. Search for Related Content PubMed PubMed Citation Articles by Capasso, G. Articles by Meyer, G.

Upregulation of apical sodium-chloride cotransporter and basolateral chloride channels is responsible for the maintenance of salt-sensitive hypertension

¹Department of Internal Medicine, Chair of Nephrology, Faculty of Medicine, Second University of Napoli, Napoli, Italy; ²Prassis Research Institute, Sigma Tau, Milan, Italy; ³Department of Physiology, University of Tuebingen, Tuebingen, Germany; ⁴Institute of Anatomy and Physiology, University of Zurich, Zurich, Switzerland; ⁵Chair of Nephrology, Ateneo Vita e Salute, S. Raffaele Hospital, Milan, Italy; ⁶Department of Pharmacology, Paracelsius Medical University, Salzburg, Austria; and ⁷Department of Biomolecular Sciences and Biotechnology, Free University of Milan, Milan, Italy

Submitted 22 July 2007 ; accepted in final form 6 May 2008

We investigated which of the NaCl transporters are involved in the maintenance of salt-sensitive hypertension. Milan hypertensive (MHS) rats were studied 3 mo after birth. In MHS, compared with normotensive strain (MNS), mRNA abundance, quantified by competitive PCR on isolated tubules, was unchanged, both for Na⁺/H⁺ isoform 3 (NHE3) and Na⁺-K⁺-2Cl^– (NKCC2), but higher (119%, n = 5, P < 0.005) for Na⁺-Cl^– (NCC) in distal convoluted tubules (DCT). These results were confirmed by Western blots, which revealed: 1) unchanged NHE3 in the cortex and NKCC2 in the outer medulla; 2) a significant increase (52%, n = 6, P < 0.001) of NCC in the cortex; 3) - and β-sodium channels [epithelial Na⁺ channel (ENaC)] unaffected in renal cortex and slightly reduced in the outer medulla, while -ENaC remained unchanged. Pendrin protein expression was unaffected. The role of NCC was reinforced by immunocytochemical studies showing increased NCC on the apical membrane of DCT cells of MHS animals, and by clearance experiments demonstrating a larger sensitivity (P < 0.001) to bendroflumethiazide in MHS rats. Kidney-specific chloride channels (ClC-K) were studied by Western blot experiments on renal cortex and by patch-clamp studies on primary culture of DCT dissected from MNS and MHS animals. Electrophysiological characteristics of ClC-K channels were unchanged in MHS rats, but the number of active channels in a patch was 0.60 ± 0.21 (n = 35) in MNS rats and 2.17 ± 0.59 (n = 23) in MHS rats (P < 0.05). The data indicate that, in salt-sensitive hypertension, there is a strong upregulation, both of NCC and ClC-K along the DCT, which explains the persistence of hypertension.

type 3 sodium/hydrogen exchanger; sodium-potassium 2 chloride cotransporter; sodium-chloride cotransporter; epithelial sodium channel; kidney-specific chloride channel; pendrin; aldosterone