Premium
Activation of Na,K,2Cl‐cotransporter stimulates outer medullary connective tissue expression
Author(s) -
Paliege Alexander,
Mutig Kerim,
Theilig Franziska,
Goligorsky Michael,
Bachmann Sebastian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1179.6
Subject(s) - endocrinology , medicine , connective tissue , extracellular matrix , chemistry , medullary cavity , extracellular , vasopressin , fibrosis , renal medulla , kidney , cotransporter , biology , biochemistry , sodium , genetics , organic chemistry
Nitric oxide (NO) deficiency stimulates renal medullary Na,K,2Cl‐cotransporter (NKCC2) activity. Chronic NO synthase inhibition has also been shown to increase the production of extracellular matrix components, thus promoting renal fibrosis. The role of NKCC2 in this process is not fully understood. We here hypothesize that chronic activation of NKCC2 leads to increased production of extracellular matrix components despite intact NO production. To test this, male adult Brattleboro rats with central diabetes insipidus were treated with the vasopressin 2 receptor analoque desmopressin (5ng/h; 5d), via osmotic minipumps. Urinary output served as a measure of treatment efficiency. NKCC2 expression in outer medullary tissue samples was determined by TaqMan real time RT PCR. Microarray analysis was used to identify differentially regulated genes. In the treated rats 24h urine output was decreased to 6% (p=.01) and outer medullary NKCC2 expression was increased to 170% (p=.013) of controls. Microarray analysis revealed increased expression of numerous extracellular matrix components including collagen I, III–VI, XII, XV and XVIII (>2fold; p<10‐5). We conclude that the activation of NKCC2 in a setting of intact local NO synthesis is associated with increased outer medullary connective tissue production. Long term studies are needed to elucidate the pathophysiological significance of this finding.