| WNK1 Regulates Vasoconstriction and Blood Pressure Response to {alpha}1-Adrenergic Stimulation in Mice. | |
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MedLine Citation:
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PMID: 21768522 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Gain-of-function mutations in the human WNK1 (with-no-lysine[K]1) gene are responsible for a monogenic form of arterial hypertension, and WNK1 polymorphisms have been associated with common essential hypertension. The role of WNK1 in renal ionic reabsorption has been established, but no investigation of its possible influence on vascular tone, an essential determinant of blood pressure, has been performed until now. WNK1 complete inactivation in the mouse is embryonically lethal. We, thus, examined in Wnk1(+/)(-) haploinsufficient adult mice whether WNK1 could regulate in vivo vascular tone and whether this was correlated with blood pressure variation. Wnk1(+/)(-) mice displayed a pronounced decrease in blood pressure responses in vivo and in vascular contractions ex vivo following α(1)-adrenergic receptor activation with no change in basal blood pressure and renal function. We also observed a major loss of the pressure-induced contractile (myogenic) response in Wnk1(+/)(-) arteries associated with a specific alteration of the smooth muscle cell contractile function. These alterations in vascular tone were associated with a decreased phosphorylation level of the WNK1 substrate SPAK (STE20/SPS1-related proline/alanine-rich kinase) and its target NKCC1 (Na(+)-K(+)-2Cl(-) cotransporter 1) in Wnk1(+/)(-) arteries. Our study identifies a novel and major role for WNK1 in maintaining in vivo blood pressure and vasoconstriction responses specific to α(1)-adrenergic receptor activation. Our findings uncover a vascular signaling pathway linking α(1)-adrenergic receptors and pressure to WNK1, SPAK, and NKCC1 and may, thus, significantly broaden the comprehension of the regulatory mechanisms of vascular tone in arterial hypertension. |
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Authors:
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Sonia Bergaya; Sébastien Faure; Véronique Baudrie; Marc Rio; Brigitte Escoubet; Philippe Bonnin; Daniel Henrion; Gervaise Loirand; Jean-Michel Achard; Xavier Jeunemaitre; Juliette Hadchouel |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-18 |
Journal Detail:
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Title: Hypertension Volume: - ISSN: 1524-4563 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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INSERM, U970, Paris Cardiovascular Research Center, Paris, France; Université Paris Descartes, Paris, France; Centre National de la Recherche Scientifique UMR 6214, INSERM U771, Angers University, Angers, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France; INSERM UMR 915, CARDIEX Platform, Nantes, France; INSERM U872, CEFI IFR02, Faculté de Médecine Xavier-Bichat, Paris, France; Université Paris Diderot, Faculté de Médecine, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris France; INSERM U965, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Paris, France; Division of Nephrology and Department of Physiology, Limoges University Hospital, Limoges, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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