title: Effect of obstructive respiratory events on blood pressure and renal perfusion in a pig model for sleep apnea.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is associated with hypertension and the progression of chronic kidney disease (CKD). Renal sympathetic innervation contributes to either condition.
  
  
  METHODS
  We investigated the effect of renal sympathetic denervation (RDN) on blood pressure (BP), renal perfusion, and neurohumoral responses during and after repetitive obstructive apneas in a pig model for OSA. BP, femoral artery, and renal artery flow were measured in 29 spontaneously breathing urethane-chloralose-anesthetized pigs. The effect of RDN (n = 14) and irbesartan (n = 3) was investigated. Repetitive tracheal occlusions for 2 minutes with applied negative tracheal pressure at -80 mbar were performed over 4 hours.
  
  
  RESULTS
  Spontaneous breathing attempts during tracheal occlusion caused an intra-apneic breathing synchronous oscillating pattern of renal flow. Renal flow oscillations were > 2-fold higher compared with femoral flow that almost showed changes proportional to the BP alterations (2.9%/mm Hg vs. 1.3%/mm Hg; P < 0.0001). A marked postapneic BP rise from 102 ± 3 to 172 ± 8 mm Hg (P < 0.00001) was associated with renal hypoperfusion (from 190 ± 24 to 70 ± 20 ml/min; P < 0.00001) occurring after application of obstructive respiratory events. RDN, but not irbesartan, inhibited postapneic BP rises and renal hypoperfusion and attenuated increased plasma renin activity and aldosterone concentration induced by repetitive tracheal occlusions. Additionally, increased urinary protein/creatinine ratio was significantly reduced by RDN, whereas intra-apneic hemodynamic changes or blood gases were not modified by RDN.
  
  
  CONCLUSIONS
  Repetitive obstructive respiratory events result in postapneic BP rises and renal hypoperfusion, as well as neurohumoral responses and increased protein/creatinine ratio. These changes are mainly sympathetically driven because they could be attenuated by RDN.
authors.affiliation: Klinik für Innere Medizin III, 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, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Benedikt
authors.initials: B
authors.lastname: Linz
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Mathias
authors.initials: M
authors.lastname: Hohl
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Schirmer
authors.affiliation: Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt, Germany.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Wirth
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003404:Creatinine / Q000652:urine; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D000077405:Irbesartan; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation; D011507:Proteinuria; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology; D012083:Renin / Q000097:blood; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology*; D013562:Sympathectomy; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000450:Aldosterone; D003404:Creatinine; D012083:Renin; D000077405:Irbesartan
keywords: blood pressure; blood pressure rise; hypertension; renal denervation; renal perfusion; sleep apnea.