Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice

Abstract Acquired forms of nephrogenic diabetes insipidus (NDI) include lithium (Li)‐induced and hypokalemia‐induced NDI. Both forms are associated with AQP2 downregulation and collecting duct (CD) cellular remodeling. Statins are cholesterol‐lowering drugs appearing to increase AQP2 membrane‐transl...

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Autores principales:	Maria L. Thomsen, Camilla Grønkjær, Anna Iervolino, Soham Rej, Francesco Trepiccione, Birgitte M. Christensen
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AQP2 hypokalemia lithium NDI statin Physiology QP1-981
Acceso en línea:	https://doaj.org/article/c1ee64309575451682d21f9fd23afefa
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spelling	oai:doaj.org-article:c1ee64309575451682d21f9fd23afefa2021-11-15T09:54:41ZAtorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice2051-817X10.14814/phy2.15111https://doaj.org/article/c1ee64309575451682d21f9fd23afefa2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15111https://doaj.org/toc/2051-817XAbstract Acquired forms of nephrogenic diabetes insipidus (NDI) include lithium (Li)‐induced and hypokalemia‐induced NDI. Both forms are associated with AQP2 downregulation and collecting duct (CD) cellular remodeling. Statins are cholesterol‐lowering drugs appearing to increase AQP2 membrane‐translocation and improve urine concentration in other NDI models. We have investigated if statins are able to prevent or rescue the Li‐induced changes in mice and in a mouse cortical CD cell line (mCCDc1l). Biotinylation assays showed that acute (1hr) atorvastatin, simvastatin, or fluvastatin increased AQP2 membrane accumulation in mCCDc1l cells showing that the cell line responds to acute statin treatment. To see whether chronic statin treatment abolish the Li effects, mCCDc1l cells were treated with 48 h Li, combined Li/atorvastatin or combined Li/simvastatin. Li reduced AQP2, but combined Li/atorvastatin or Li/simvastatin did not prevent AQP2 downregulation. In mice, chronic (21 days) Li increased urine output and reduced urine osmolality, but combined Li/atorvastatin did not prevent these effects. In inner medulla (IM), Li reduced total AQP2 and increased pS261‐AQP2. Combined Li/atorvastatin did not abolish these changes. Atorvastatin did not prevent a Li‐induced increase in intercalated cells and proliferation in IM. In mice with already established NDI, atorvastatin had no effect on the Li‐induced changes either. Mice subjected to 14 days of potassium‐deficient diet developed polyuria and AQP2 downregulation in IM. Co‐treatment with atorvastatin did not prevent this. In conclusion, atorvastatin does not appear to be able to prevent or rescue Li‐NDI or to prevent hypokalemic‐induced NDI.Maria L. ThomsenCamilla GrønkjærAnna IervolinoSoham RejFrancesco TrepiccioneBirgitte M. ChristensenWileyarticleAQP2hypokalemialithiumNDIstatinPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AQP2 hypokalemia lithium NDI statin Physiology QP1-981
spellingShingle	AQP2 hypokalemia lithium NDI statin Physiology QP1-981 Maria L. Thomsen Camilla Grønkjær Anna Iervolino Soham Rej Francesco Trepiccione Birgitte M. Christensen Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
description	Abstract Acquired forms of nephrogenic diabetes insipidus (NDI) include lithium (Li)‐induced and hypokalemia‐induced NDI. Both forms are associated with AQP2 downregulation and collecting duct (CD) cellular remodeling. Statins are cholesterol‐lowering drugs appearing to increase AQP2 membrane‐translocation and improve urine concentration in other NDI models. We have investigated if statins are able to prevent or rescue the Li‐induced changes in mice and in a mouse cortical CD cell line (mCCDc1l). Biotinylation assays showed that acute (1hr) atorvastatin, simvastatin, or fluvastatin increased AQP2 membrane accumulation in mCCDc1l cells showing that the cell line responds to acute statin treatment. To see whether chronic statin treatment abolish the Li effects, mCCDc1l cells were treated with 48 h Li, combined Li/atorvastatin or combined Li/simvastatin. Li reduced AQP2, but combined Li/atorvastatin or Li/simvastatin did not prevent AQP2 downregulation. In mice, chronic (21 days) Li increased urine output and reduced urine osmolality, but combined Li/atorvastatin did not prevent these effects. In inner medulla (IM), Li reduced total AQP2 and increased pS261‐AQP2. Combined Li/atorvastatin did not abolish these changes. Atorvastatin did not prevent a Li‐induced increase in intercalated cells and proliferation in IM. In mice with already established NDI, atorvastatin had no effect on the Li‐induced changes either. Mice subjected to 14 days of potassium‐deficient diet developed polyuria and AQP2 downregulation in IM. Co‐treatment with atorvastatin did not prevent this. In conclusion, atorvastatin does not appear to be able to prevent or rescue Li‐NDI or to prevent hypokalemic‐induced NDI.
format	article
author	Maria L. Thomsen Camilla Grønkjær Anna Iervolino Soham Rej Francesco Trepiccione Birgitte M. Christensen
author_facet	Maria L. Thomsen Camilla Grønkjær Anna Iervolino Soham Rej Francesco Trepiccione Birgitte M. Christensen
author_sort	Maria L. Thomsen
title	Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
title_short	Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
title_full	Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
title_fullStr	Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
title_full_unstemmed	Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
title_sort	atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c1ee64309575451682d21f9fd23afefa
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Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice

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