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Role of the Primary Cilia on the Macula Densa and Thick Ascending Limbs in Regulation of Sodium Excretion and Hemodynamics.
Song, Jiangping; Wang, Lei; Fan, Fan; Wei, Jin; Zhang, Jie; Lu, Yan; Fu, Yiling; Wang, Shaohui; Juncos, Luis A; Liu, Ruisheng.
Affiliation
  • Song J; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Wang L; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Fan F; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Wei J; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Zhang J; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Lu Y; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Fu Y; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Wang S; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Juncos LA; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
  • Liu R; From the Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa (J.S., L.W., J.W., J.Z., S.W., R.L.); State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
Hypertension ; 70(2): 324-333, 2017 08.
Article in En | MEDLINE | ID: mdl-28607127
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2CRE; IFT88Δ/flox), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus. Deletion of the cilia reduced NO production by 56% and 42% in the macula densa and TAL, respectively. NO generation by the macula densa was inhibited by both a nonselective and a selective nitric oxide synthesis inhibitors, whereas TAL-produced NO was inhibited by a nonselective and not by a selective NO synthesis 1 inhibitor. The tubuloglomerular feedback response was enhanced in the KO mice both in vitro measured with isolated perfused juxtaglomerular apparatuses and in vivo measured with micropuncture. In response to an acute volume expansion, the KO mice exhibited limited glomerular filtration rate elevation and impaired sodium excretion compared with the wild-type mice. The mean arterial pressure measured with telemetry was the same for wild-type and KO mice fed a normal salt diet. After a high salt diet, the mean arterial pressure increased by 17.4±1.6 mm Hg in the KO mice. On the basis of these findings, we concluded that the primary cilia on the macula densa and TAL play an essential role in the control of sodium excretion and blood pressure.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Blood Pressure / Sodium Chloride / Cilia / Renal Elimination / Hemodynamics Type of study: Prognostic_studies Limits: Animals Language: En Journal: Hypertension Year: 2017 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Blood Pressure / Sodium Chloride / Cilia / Renal Elimination / Hemodynamics Type of study: Prognostic_studies Limits: Animals Language: En Journal: Hypertension Year: 2017 Document type: Article Country of publication: United States