title: A nitric oxide-generating beta-blocking agent prevents renal injury in the rat remnant kidney model. Comparative study of two beta-blocking drugs, nipradilol and propranolol.
abstract: BACKGROUND
  The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether beta-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis.
  
  
  METHODS
  Nipradilol, a beta-blocker with an ONO(2) group (5, 10 or 15 mg/kg/day) and propranolol, a beta-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U(NOx)) and cyclic GMP (U(cGMP)).
  
  
  RESULTS
  Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U(NOx) in comparison with the sham-operated rats. Nipradilol increased U(NOx) and U(cGMP) significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U(NOx). The addition of nipradilol increased U(NOx) and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect.
  
  
  CONCLUSIONS
  These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The beta-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.
authors.affiliation: Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. y-tkmt@hyo-med.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takamitsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nishihara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hasuike
authors.forename: Masaaki
authors.initials: M
authors.lastname: Izumi
authors.forename: Toru
authors.initials: T
authors.lastname: Inoue
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hiraoka
authors.forename: Reiko
authors.initials: R
authors.lastname: Itahana
authors.forename: Koji
authors.initials: K
authors.lastname: Miyagawa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D006152:Cyclic GMP / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000517:prevention & control; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000652:urine; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D012083:Renin / Q000097:blood
chemical_list: D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D011412:Propanolamines; D009569:Nitric Oxide; D011433:Propranolol; D019001:Nitric Oxide Synthase; D012083:Renin; C036089:nipradilol; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester