title: Vasopeptidase Inhibition Corrects the Structure and Function of the Small Arteries in Experimental Renal Insufficiency.
abstract: BACKGROUND
  We studied whether vasopeptidase inhibition corrects the structure and function of the small arteries in experimental chronic renal insufficiency (CRI).
  
  
  METHODS
  After 5/6 nephrectomy (NX) surgery was performed on rats, there was a 14-week follow-up, allowing CRI to become established. Omapatrilat (40 mg/kg/day in chow) was then given for 8 weeks, and the small mesenteric arterial rings were investigated in vitro using wire and pressure myographs.
  
  
  RESULTS
  Plasma and ventricular B-type natriuretic peptide (BNP) concentrations were increased 2- to 2.7-fold, while systolic blood pressure (BP) increased by 32 mm Hg after NX. Omapatrilat treatment normalized the BNP and reduced the BP by 45 mm Hg in the NX rats. Endothelium-dependent vasorelaxation was impaired but the response to acetylcholine was normalized after omapatrilat treatment. Vasorelaxations induced by nitroprusside, isoprenaline and levcromakalim were enhanced after omapatrilat, and the responses were even more pronounced than in untreated sham-operated rats. Arterial wall thickness and wall-to-lumen ratio were increased after NX, whereas omapatrilat normalized these structural features and improved the strain-stress relationship in the small arteries; this suggests improved arterial elastic properties.
  
  
  CONCLUSIONS
  Omapatrilat treatment reduced BP, normalized volume overload, improved vasorelaxation and corrected the dimensions and passive elastic properties of the small arteries in the NX rats. Therefore, we consider vasopeptidase inhibition to be an effective treatment for CRI-induced changes in the small arteries.
authors.affiliation: Schools of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Haltia
authors.forename: Suvi
authors.initials: S
authors.lastname: Törmänen
authors.forename: Arttu
authors.initials: A
authors.lastname: Eräranta
authors.forename: Jarkko
authors.initials: J
authors.lastname: Jokihaara
authors.forename: Klaus
authors.initials: K
authors.lastname: Nordhausen
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Ilkka
authors.initials: I
authors.lastname: Tikkanen
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009392:Nephrectomy; D011725:Pyridines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013841:Thiazepines / Q000494:pharmacology*; D066253:Vascular Remodeling / Q000187:drug effects*; D059289:Vascular Stiffness / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011725:Pyridines; D013841:Thiazepines; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; C106266:omapatrilat