title: Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy.
abstract: BACKGROUND
  We have previously demonstrated the increased salt sensitivity of blood pressure (BP) in diabetic patients with early nephropathy. Here, we examined the effects of an angiotensin II receptor blocker (ARB) on salt sensitivity and renal oxidative stress or nitric oxide (NO) in those patients.
  
  
  METHODS
  Type 2 diabetic patients with (n = 6) and without (n = 6) microalbuminuria were studied on a high-salt diet for one week and on a salt-restricted diet for one week. The study was repeated in the patients with microalbuminuria during treatment with an ARB, valsartan (80 mg/day). Salt sensitivity was assessed from the BP/sodium excretion curve. Urinary excretion rates of NOx, 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress, and plasma tetrahydrobiopterin as a cofactor for NO synthase were measured.
  
  
  RESULTS
  Compared with diabetic patients without microalbuminuria, patients with microalbuminuria showed greater salt sensitivity and lower urinary excretion of NOx. In the patients with microalbuminuria, treatment with valsartan reduced salt sensitivity in association with increased NOx excretion, reduced 8-hydroxy-2,-deoxyguanosine excretion, and increased plasma tetrahydrobiopterin levels.
  
  
  CONCLUSIONS
  These data support the hypothesis that ARBs reduce the salt sensitivity of BP by decreasing renal oxidative stress and restoring NO activity in diabetic patients with microalbuminuria.
authors.affiliation: Department of Nephrology and Hypertension, Osaka City General Hospital, Japan. masachan@msic.med.osaka-cu.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okada
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Konishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Isseki
authors.initials: I
authors.lastname: Maeda
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kitabayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shirahashi
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000652:urine; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D009566:Nitrates; D009573:Nitrites; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D001708:Biopterins; D009569:Nitric Oxide; D000068756:Valsartan; D000080242:8-Hydroxy-2'-Deoxyguanosine; C003402:sapropterin; D003849:Deoxyguanosine; D014633:Valine