{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:06Z","timestamp":1787017626729,"version":"build-2736575974"},"reference-count":50,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:p>\n                    Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fischer 344 X Brown Norway (F344BN) rats for 8 wk with diets containing either normal (NF, 4%) or high (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50\u2013125%) and the renal outer medullary potassium channel (106%), as well as increased natriuretic response to furosemide (20\u201340%). To test the role of oxidative stress in this response, in study 2, rats were fed the NF or HF diet plus plain drinking water, or water containing N\n                    <jats:sup>G<\/jats:sup>\n                    -nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor (100 mg\/l), or tempol, a superoxide dismutase mimetic (1 mmol\/l). The combination of tempol with HF nullified the increase in medullary NKCC2, while l-NAME with HF led to the highest expression of medullary NKCC2 (to 498% of NF mean). However, neither of these drugs dramatically affected the elevated natriuretic response to furosemide with HF. Finally, l-NAME led to a marked increase in blood pressure (measured by radiotelemetry), which was significantly enhanced with HF. Mean arterial blood pressure at 7 wk was as follows (mmHg): NF, 100 \u00b1 2; NF plus l-NAME, 122 \u00b1 3; and HF plus l-NAME, 131 \u00b1 2. Overall, HF feeding increased the abundance of NKCC2. Inappropriately high sodium reabsorption in the thick ascending limb via NKCC2 may contribute to hypertension with insulin resistance.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.90484.2008","type":"journal-article","created":{"date-parts":[[2009,2,4]],"date-time":"2009-02-04T20:55:59Z","timestamp":1233780959000},"page":"F762-F770","source":"Crossref","is-referenced-by-count":19,"title":["Abundance of the Na-K-2Cl cotransporter NKCC2 is increased by high-fat feeding in Fischer 344 X Brown Norway (F1) rats"],"prefix":"10.1152","volume":"296","author":[{"given":"Shahla","family":"Riazi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swasti","family":"Tiwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Rash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Ecelbarger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1139\/y99-060"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282f2f0f3"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.10.002"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.23.3.308"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00353.x"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.4.F639"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1992.262.3.F454"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00608.2007"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.554"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000103629.01745.59"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00388.2002"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Ecelbarger CA\n                      , Kim GH, Knepper MA, Liu J, Tate M, Welling PA, Wade JB.\n                      Regulation of potassium channel Kir 1.1 (ROMK) abundance in the thick ascending limb of Henle's loop.\n                      J Am Soc Nephrol\n                      12\n                      : 10\u201318, 2001.","DOI":"10.1681\/ASN.V12110"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F46"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Ecelbarger CA\n                      , Knepper MA, Verbalis JG.\n                      Increased abundance of distal sodium transporters in rat kidney during vasopressin escape.\n                      J Am Soc Nephrol\n                      12\n                      : 207\u2013217, 2001.","DOI":"10.1681\/ASN.V122207"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1159\/000022098"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200501000-00003"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.3.356"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1046\/j.0001-6772.2003.01203.x"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303435200"},{"key":"R20","unstructured":"Grundy SM\n                      .\n                      Metabolic syndrome: therapeutic considerations.\n                      Handb Exp Pharmacol\n                      : 107\u2013133, 2005."},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02077-5"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00383.2006"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1081\/CEH-100107389"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.5.1091"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)01707-1"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Jonassen TE\n                      , Brond L, Torp M, Graebe M, Nielsen S, Skott O, Marcussen N, Christensen S.\n                      Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis.\n                      Am J Physiol Renal Physiol\n                      284\n                      : F555\u2013F563, 2003.","DOI":"10.1152\/ajprenal.00258.2002"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1997.273.2.R568"},{"key":"R28","doi-asserted-by":"crossref","unstructured":"Juncos R\n                      , Garvin JL.\n                      Superoxide enhances Na-K-2Cl cotransporter activity in the thick ascending limb.\n                      Am J Physiol Renal Physiol\n                      288\n                      : F982\u2013F987, 2005.","DOI":"10.1152\/ajprenal.00348.2004"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006060606"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000174989.39003.58"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.10.009"},{"key":"R32","unstructured":"Kunes J\n                      , Hojna S, Kadlecova M, Dobesova Z, Rauchova H, Vokurkova M, Loukotova J, Pechanova O, Zicha J.\n                      Altered balance of vasoactive systems in experimental hypertension: the role of relative NO deficiency.\n                      Physiol Res\n                      53\n                      ,\n                      Suppl\n                      1: S23\u2013S34, 2004."},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/51A.1.B54"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000113295.31481.36"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.11.1768"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00334.2001"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.0075.2001"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1210\/rp.59.1.225"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1159\/000093783"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/S1550-8579(06)80219-6"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8807com"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.1.424"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00177.2004"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00063.2004"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.058008"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(03)00128-7"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01490-7"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02231-2"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/54.11.B492"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000251907.93298.44"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.90484.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T23:19:39Z","timestamp":1633043979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.90484.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1152\/ajprenal.90484.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.90484.2008","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4]]}}}