Endothelin-1 mediates natriuresis but not polyuria during vitamin D-induced acute hypercalcaemia

Autor: Tokonami, Natsuko, Cheval, Lydie, Monnay, Isabelle, Meurice, Guillaume, Loffing, Johannes, Feraille, Eric, Houillier, Pascal
Přispěvatelé: University of Zurich, Houillier, Pascal, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Métabolisme et physiologie rénales (ERL 8228), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Plateforme de Génomique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Fribourg = University of Fribourg (UNIFR), Fondation pour Recherche Médicale [Geneva], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), CNRS ERL 8228 - Laboratoire de physiologie rénale et tubulopathies, 75006, Paris, France. (TIR), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Fribourg
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
MESH: Endothelin-1
endocrine system diseases
10017 Institute of Anatomy
[SDV]Life Sciences [q-bio]
MESH: Natriuresis
Natriuresis
610 Medicine & health
Inbred C57BL
Polyuria/metabolism/urine
Cell Line
MESH: Hypercalcemia
Mice
MESH: Vitamin D
MESH: Mice
Inbred C57BL
Humans
Animals
MESH: Animals
MESH: Cell Line
Transformed
Vitamin D
ddc:612
Renal
MESH: Mice
Cell Line
Transformed
Hypercalcemia/chemically induced/metabolism/urine
Endothelin-1
Polyuria
Sodium
distal nephron
nutritional and metabolic diseases
hypercalcemia
1314 Physiology
MESH: Polyuria
MESH: Male
Natriuresis/drug effects/physiology
Mice
Inbred C57BL
Kidney Tubules
Transformed
Kidney Tubules/drug effects/metabolism
Acute Disease
MESH: Kidney Tubules
MESH: Acute Disease
570 Life sciences
biology
Endothelin-1/physiology
Calcium
endothelin
odium balance
Vitamin D/toxicity
Perspectives
Zdroj: The Journal of Physiology
The Journal of Physiology, 2017, 595 (8), pp.2535-2550. ⟨10.1113/JP273610⟩
The Journal of Physiology, Wiley, 2017, 595 (8), pp.2535-2550. ⟨10.1113/JP273610⟩
The Journal of Physiology, Vol. 595, No 8 (2017) pp. 2535-2550
ISSN: 0022-3751
1469-7793
DOI: 10.5167/uzh-137428
Popis: Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria. Vitamin D-treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited. We have identified an original pathway that specifically mediates the effects of vitamin D-induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling.Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT-treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT-treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D-induced hypercalcaemia increases the renal production of ET-1 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria.
Databáze: OpenAIRE
Externí odkaz: