Aldosterone-independent regulation of the epithelial Na⁺ channel (ENaC) by vasopressin in adrenalectomized mice
The epithelial Na ⁺ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin–angiotensin–aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (25), p.10095-10100 |
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| creator | Mironova, Elena Bugaj, Vladislav Roos, Karl P Kohan, Donald E Stockand, James D |
| description | The epithelial Na ⁺ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin–angiotensin–aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V ₂ AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na ⁺ balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency. |
| doi_str_mv | 10.1073/pnas.1201978109 |
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We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V ₂ AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na ⁺ balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1201978109</identifier><identifier>PMID: 22665796</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>absorption ; Adrenal insufficiency ; Adrenalectomy ; aldosterone ; Aldosterone - physiology ; Animals ; Antibodies ; Arginine Vasopressin - blood ; Arginine Vasopressin - physiology ; Biological Sciences ; blood pressure ; Epithelial Sodium Channels - physiology ; Excretion ; Gene expression ; Hormones ; hyponatremia ; Mice ; Mineralocorticoids ; Physiological regulation ; Proteins ; Receptors ; Rodents ; Sodium ; sodium channels ; Steroids ; Tap water ; vasopressin</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-06, Vol.109 (25), p.10095-10100</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 19, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-ef64338ddfb3f5f3872c75b2a2e10c88adc6e6169d379133308314a1928458773</citedby><cites>FETCH-LOGICAL-c591t-ef64338ddfb3f5f3872c75b2a2e10c88adc6e6169d379133308314a1928458773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/25.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41602805$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41602805$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22665796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mironova, Elena</creatorcontrib><creatorcontrib>Bugaj, Vladislav</creatorcontrib><creatorcontrib>Roos, Karl P</creatorcontrib><creatorcontrib>Kohan, Donald E</creatorcontrib><creatorcontrib>Stockand, James D</creatorcontrib><title>Aldosterone-independent regulation of the epithelial Na⁺ channel (ENaC) by vasopressin in adrenalectomized mice</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The epithelial Na ⁺ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin–angiotensin–aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V ₂ AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na ⁺ balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency.</description><subject>absorption</subject><subject>Adrenal insufficiency</subject><subject>Adrenalectomy</subject><subject>aldosterone</subject><subject>Aldosterone - physiology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Arginine Vasopressin - blood</subject><subject>Arginine Vasopressin - physiology</subject><subject>Biological Sciences</subject><subject>blood pressure</subject><subject>Epithelial Sodium Channels - physiology</subject><subject>Excretion</subject><subject>Gene expression</subject><subject>Hormones</subject><subject>hyponatremia</subject><subject>Mice</subject><subject>Mineralocorticoids</subject><subject>Physiological regulation</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Rodents</subject><subject>Sodium</subject><subject>sodium channels</subject><subject>Steroids</subject><subject>Tap water</subject><subject>vasopressin</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9u1DAQxiMEokvhzAmwxKUc0o7txLEvSNWq_JGqcoCeLW8y2fUqa6d2UqnceC0ehyfBIcsWuCBZM4f5-ZsZf86y5xROKVT8rHcmnlIGVFWSgnqQLVKkuSgUPMwWAKzKZcGKo-xJjFsAUKWEx9kRY0KUlRKL7Oa8a3wcMHiHuXUN9piCG0jA9diZwXpHfEuGDRLsbUqdNR25Mj--fSf1xjiHHTm5uDLLN2R1R25N9H3AGK0j6ZgmoDMd1oPf2a_YkJ2t8Wn2qDVdxGf7fJxdv7v4svyQX356_3F5fpnXpaJDjq0oOJdN0654W7ZcVqyuyhUzDCnUUpqmFiioUA2vFOWcg-S0MFQxWZSyqvhx9nbW7cfVDps6LRVMp_tgdybcaW-s_rvi7Eav_a1OXVmhJoGTvUDwNyPGQe9srLHrjEM_Rk0lcCqEAP5_FBgtSlZCkdDX_6BbP4b0SjPFRcV_9T6bqTr4GAO2h7kp6Ml5PTmv751PN17-ue6B_211AsgemG7eyynNypTS10jIixnZxsGHA1NQAUzCVH8111vjtVkHG_X15zSCAKBMShD8Jw3lyCA</recordid><startdate>20120619</startdate><enddate>20120619</enddate><creator>Mironova, Elena</creator><creator>Bugaj, Vladislav</creator><creator>Roos, Karl P</creator><creator>Kohan, Donald E</creator><creator>Stockand, James D</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20120619</creationdate><title>Aldosterone-independent regulation of the epithelial Na⁺ channel (ENaC) by vasopressin in adrenalectomized mice</title><author>Mironova, Elena ; Bugaj, Vladislav ; Roos, Karl P ; Kohan, Donald E ; Stockand, James D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-ef64338ddfb3f5f3872c75b2a2e10c88adc6e6169d379133308314a1928458773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>absorption</topic><topic>Adrenal insufficiency</topic><topic>Adrenalectomy</topic><topic>aldosterone</topic><topic>Aldosterone - physiology</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Arginine Vasopressin - blood</topic><topic>Arginine Vasopressin - physiology</topic><topic>Biological Sciences</topic><topic>blood pressure</topic><topic>Epithelial Sodium Channels - physiology</topic><topic>Excretion</topic><topic>Gene expression</topic><topic>Hormones</topic><topic>hyponatremia</topic><topic>Mice</topic><topic>Mineralocorticoids</topic><topic>Physiological regulation</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Rodents</topic><topic>Sodium</topic><topic>sodium channels</topic><topic>Steroids</topic><topic>Tap water</topic><topic>vasopressin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mironova, Elena</creatorcontrib><creatorcontrib>Bugaj, Vladislav</creatorcontrib><creatorcontrib>Roos, Karl P</creatorcontrib><creatorcontrib>Kohan, Donald E</creatorcontrib><creatorcontrib>Stockand, James D</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mironova, Elena</au><au>Bugaj, Vladislav</au><au>Roos, Karl P</au><au>Kohan, Donald E</au><au>Stockand, James D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aldosterone-independent regulation of the epithelial Na⁺ channel (ENaC) by vasopressin in adrenalectomized mice</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-06-19</date><risdate>2012</risdate><volume>109</volume><issue>25</issue><spage>10095</spage><epage>10100</epage><pages>10095-10100</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The epithelial Na ⁺ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin–angiotensin–aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V ₂ AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na ⁺ balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22665796</pmid><doi>10.1073/pnas.1201978109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | absorption Adrenal insufficiency Adrenalectomy aldosterone Aldosterone - physiology Animals Antibodies Arginine Vasopressin - blood Arginine Vasopressin - physiology Biological Sciences blood pressure Epithelial Sodium Channels - physiology Excretion Gene expression Hormones hyponatremia Mice Mineralocorticoids Physiological regulation Proteins Receptors Rodents Sodium sodium channels Steroids Tap water vasopressin |
| title | Aldosterone-independent regulation of the epithelial Na⁺ channel (ENaC) by vasopressin in adrenalectomized mice |
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