Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

Abstract

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) alpha- and beta-sodium channels [epithelial Na+ channel (ENaC)] unaffected in renal cortex and slightly reduced in the outer medulla, while gamma-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.

Useful keywords (using NLM MeSH Indexing)

Aldosterone/metabolism

Animals

Chloride Channels/genetics

Chloride Channels/metabolism*

Chloride-Bicarbonate Antiporters/metabolism

Disease Models, Animal

Epithelial Sodium Channels/metabolism

Hypertension/genetics

Hypertension/metabolism*

Hypertension/physiopathology

Kidney Cortex/metabolism*

Kidney Cortex/physiopathology

Kidney Medulla/metabolism*

Kidney Medulla/physiopathology

Patch-Clamp Techniques

RNA, Messenger/metabolism

Rats

Rats, Inbred Strains

Sodium Chloride Symporters/genetics

Sodium Chloride Symporters/metabolism*

Sodium Chloride, Dietary/adverse effects

Sodium-Hydrogen Antiporter/metabolism

Sodium-Potassium-Chloride Symporters/metabolism

Up-Regulation*

Find related publications in this database (Keywords)