title: Effect of aliskiren on vascular remodelling in small retinal circulation.
abstract: BACKGROUND
  In hypertension, changes in small arterial structure are characterized by an increased wall-to-lumen ratio (WLR). These adaptive processes are modulated by the rennin-angiotensin system. It is unclear whether direct renin inhibitors exert protective effects on small arteries in hypertensive patients.
  
  
  METHODS
  In this double-blind, randomized, placebo-controlled study (http://www.clinicaltrials.gov: NCT01318395), 114 patients with primary hypertension were randomized to additional therapy with either placebo or aliskiren 300 mg for 8 weeks after 4 weeks of standardized open-label treatment with valsartan 320 mg (run-in phase). Parameter of arteriolar remodelling was WLR of retinal arterioles (80 - 140 μm) assessed noninvasively and in vivo by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). In addition, pulse wave analysis (SphygmoCor, AtCor Medical, Australia) and pulse pressure (PP) amplification were determined.
  
  
  RESULTS
  In the whole study population, no clear effect of additional therapy with aliskiren on vascular parameters was documented. When analyses were restricted to patients with vascular remodelling, defined by a median of WLR more than 0.3326 (n = 57), WLR was reduced after 8 weeks by the treatment with aliskiren compared with placebo (-0.044 ± 0.07 versus 0.0043 ± 0.07, P = 0.015). Consistently, after 8 weeks of on-top treatment with aliskiren, there was an improvement of PP amplification compared with placebo (0.025 ± 0.07 versus -0.034 ± 0.08, P = 0.013), indicative of less stiff arteries in the peripheral circulation.
  
  
  CONCLUSIONS
  Thus, our data indicate that treatment with aliskiren, given on top of valsartan therapy, improves altered vascular remodelling in hypertensive patients.
authors.affiliation: aDepartment of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany bDepartment of Pathophysiology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jumar
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Iris
authors.initials: I
authors.lastname: Kistner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Friedrich
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Harazny
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D001794:Blood Pressure; D004311:Double-Blind Method; D000075222:Essential Hypertension; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D000068756:Valsartan / Q000627:therapeutic use; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; C446481:aliskiren; D000068756:Valsartan