title: Short-term treatment with a beta-blocker with vasodilative capacities improves intrarenal endothelial function in experimental renal failure.
abstract: OBJECTIVE
  In patients with renal disease the cardiovascular risk is greatly increased, and endothelial dysfunction is assumed to play a pivotal role in this process. Therefore we compared treatment effects of a beta-blocker with additional vasodilatory capacities (nebivolol) and a beta-blocker lacking these actions (metoprolol) on intrarenal and coronary vascular function in a rat model of renal failure with hypertension.
  
  
  METHODS
  Renal failure was induced by 5/6-nephrectomy (Nx) and analyzed after 4 weeks in Wistar rats. Untreated Nx, Nx/nebivolol 6 mg/d (Nx-Nebi); Nx/metoprolol 60 mg/d (Nx-Meto) and sham-operated (Sham) animals were studied. Isolated small renal and coronary arteries were investigated for endothelium-dependent relaxation to acetylcholine (ACh) and for the contribution of the endothelial mediators NO and endothelium-derived hyperpolarizing factor (EDHF).
  
  
  RESULTS
  Systolic blood pressure (SBP) was significantly increased in Nx, Nx-Nebi, and Nx-Meto (168+/-5, 153+/-3, and 162+/-6 mmHg) compared to Sham (138+/-3 mmHg, p<0.05, respectively). The increase in albuminuria of Nx (120-fold vs. Sham, p<0.0001) was almost (-85%) normalized by nebivolol compared to Sham (p<0.05), whereas metoprolol induced no significant effect. Renal arteries showed significantly increased Ach-relaxation in Nx and Nx-Nebi (Emax 86+/-4% and 76+/-7%, p<0.05) due to an increase in EDHF-mediated dilation (Emax_EDHF 78+/-7% and 73+/-6%) compared to Sham (Emax 54+/-4% and Emax_EDHF 44+/-6%) and Nx-Meto (Emax 42+/-12% and Emax_EDHF 18+/-5%). ACh-relaxation in coronary arteries was similar between groups but the contribution of NO (relative to EDHF) was strongly increased by nebivolol.
  
  
  CONCLUSIONS
  The present findings offer an explanation of the nephroprotective effect of intrarenal endothelial function in renal failure.
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Charité Centrum für Therapieforschung, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Gschwend
authors.forename: Marcel Bernhard
authors.initials: MB
authors.lastname: Haug
authors.forename: Marc
authors.initials: M
authors.lastname: Nierhaus
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Roland
authors.initials: R
authors.lastname: Vetter
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Orzechowski
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scholze
authors.forename: Lars
authors.initials: L
authors.lastname: Rothermund
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000503:physiopathology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D003404:Creatinine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D000068577:Nebivolol; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D001685:Biological Factors; D004983:Ethanolamines; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D000068577:Nebivolol; D009599:Nitroprusside; D009569:Nitric Oxide; D003404:Creatinine; D000109:Acetylcholine