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NGAL is a Novel Target in Hypertension by Modulating the NCC-Mediated Renal Na Balance.
Bonnard, Benjamin; El Moghrabi, Soumaya; Ueda, Kohei; Lattenist, Lionel; Soulie, Matthieu; López-Andrés, Natalia; Xhaard, Constance; Shimosawa, Tatsuo; Rossignol, Patrick; Jaisser, Frédéric.
Afiliación
  • Bonnard B; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, France (B.B., S.E.M., K.U., L.L., M.S., F.J.).
  • El Moghrabi S; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, France (B.B., S.E.M., K.U., L.L., M.S., F.J.).
  • Ueda K; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, France (B.B., S.E.M., K.U., L.L., M.S., F.J.).
  • Lattenist L; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, France (B.B., S.E.M., K.U., L.L., M.S., F.J.).
  • Soulie M; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, France (B.B., S.E.M., K.U., L.L., M.S., F.J.).
  • López-Andrés N; Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (N.L.-A.).
  • Xhaard C; Universite de Lorraine, Centre d'Investigations Cliniques-1433, Inserm U1116, CHRU Nancy, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (C.X., P.R.).
  • Shimosawa T; Medicine and nephrology-dialysis departments, Princess Grace Hospital, and Monaco Private Hemodialysis Centre, Monaco (C.X., P.R., F.J.).
  • Rossignol P; Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita, Chiba, Japan (T.S.).
  • Jaisser F; Universite de Lorraine, Centre d'Investigations Cliniques-1433, Inserm U1116, CHRU Nancy, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (C.X., P.R.).
Hypertension ; 80(9): 1860-1870, 2023 09.
Article en En | MEDLINE | ID: mdl-37377014
BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2-knockout mice (lcn2 KO) fed with low-Na diet (0Na). RESULTS: we show that NGAL plasma levels positively correlate with systolic blood pressure, whereas they negatively correlate with urinary Na excretion in subjects of the STANISLAS cohort. Prolonged feeding of lcn2 KO mice with a 0Na diet induced lower systolic blood pressure than that of the control group (wildtype), suggesting a role for NGAL/lcn2 in Na-balance homeostasis. Short-term or prolonged 0Na increased Na-Cl cotransporter (NCC) phosphorylation in the cortex of wildtype mice, which was prevented in lcn2 KO mice. Recombinant mouse lcn2 injections in lcn2 KO mice induced NCC phosphorylation in the kidney cortex, associated with decreased urinary Na excretion. Ex vivo experiments using kidney slices from lcn2 KO mice showed increased NCC phosphorylation by recombinant murine lcn2. In addition, recombinant murine lcn2 induced activation of CamK2ß (calcium/calmodulin-dependent protein kinase II ß subunit) phosphorylation in lcn2 KO mice and in kidney slices, providing an underlying mechanism involved in lcn2-induced NCC phosphorylation. Indeed, the inhibition of CamK2ß prevented NCC phosphorylation induced by recombinant lcn2 in kidney slices. CONCLUSIONS: we highlight a novel role of NGAL/lcn2 as a modulator of the activity of the renal sodium transporter NCC affecting salt-sensitive blood pressure.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aldosterona / Hipertensión Límite: Animals Idioma: En Revista: Hypertension Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aldosterona / Hipertensión Límite: Animals Idioma: En Revista: Hypertension Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos