title: Progression of kidney injury and cardiac remodeling in obese spontaneously hypertensive rats: the role of renal sympathetic innervation.
abstract: BACKGROUND
  Hypertension and metabolic syndrome (MetS) are associated with increased sympathetic activation possibly contributing to the progression of renal damage and cardiac remodeling. Renal sympathetic denervation (RDN) decreases sympathetic renal efferent and afferent nerve activity.
  
  
  METHODS
  Obese spontaneously hypertensive rats (SHRs-ob) were subjected to RDN at the age of 34 weeks (SHRs-ob + RDN) and were compared with sham-operated SHRs-ob and their normotensive lean controls (Ctrs). Blood pressure was measured by telemetry. Kidney and heart function were determined by magnetic resonance imaging (MRI). Renal and cardiac remodeling were characterized by immunohistochemical analyses. Animals were killed at the age of 48 weeks.
  
  
  RESULTS
  In SHRs-ob, RDN attenuated the progressive increase in blood pressure and preserved a mean blood pressure of 156±7mm Hg compared with 220±8mm Hg in sham-operated SHRs-ob at 100 days after RDN, whereas heart rate, body weight, and metabolic parameters remained unchanged. Renal catecholamine and tyrosine hydroxylase levels were significantly reduced after RDN, suggesting effective renal denervation. Progression of renal dysfunction as characterized by increased urinary albumin/creatinine ratio and reduced glomerular filtration rate were attenuated by RDN. In SHRs-ob, renal perfusion was significantly reduced and normalized by RDN. Cardiac fibrosis and cardiac diastolic dysfunction measured by MRI and invasive pressure measurements were significantly attenuated by RDN.
  
  
  CONCLUSIONS
  In SHRs-ob, progressive increase in blood pressure and progression of renal injury and cardiac remodelling are mediated by renal sympathetic activation as they were attenuated by RDN.
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; dominik.linz@uks.eu.
authors.forename: Dominik
authors.initials: D
authors.lastname: Linz
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Mathias
authors.initials: M
authors.lastname: Hohl
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schütze
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: Klinik für Innere Medizin IV, Nephrologie und Hypertension, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Benedikt
authors.initials: B
authors.lastname: Linz
authors.affiliation: Sanofi-Aventis, Diabetes Division and BioImaging, Frankfurt, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Hübschle
authors.affiliation: Sanofi-Aventis, Diabetes Division and BioImaging, Frankfurt, Germany;
authors.forename: Hans-Paul
authors.initials: HP
authors.lastname: Juretschke
authors.affiliation: Experimental and Clinical Research Center (Campus Buch), Berlin, Germany;
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Zentrallabor, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Sanofi-Aventis, Diabetes Division and BioImaging, Frankfurt, Germany;
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rütten
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000378:metabolism*; D013562:Sympathectomy; D013564:Sympathetic Nervous System; D020257:Ventricular Remodeling
chemical_list: D003404:Creatinine
keywords: blood pressure; heart injury; hypertension; metabolic syndrome; obese spontaneously hypertensive rats; renal dysfunction; renal sympathetic denervation.