Document Detail


Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy.
MedLine Citation:
PMID:  22859713     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: 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. Patients and 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:
Masahito Imanishi; Noriyuki Okada; Yoshio Konishi; Takashi Morikawa; Isseki Maeda; Chizuko Kitabayashi; Masahiro Masada; Nobuo Shirahashi; Christopher S Wilcox; Akira Nishiyama
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-02
Journal Detail:
Title:  Journal of the renin-angiotensin-aldosterone system : JRAAS     Volume:  14     ISSN:  1752-8976     ISO Abbreviation:  J Renin Angiotensin Aldosterone Syst     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-09-18     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  100971636     Medline TA:  J Renin Angiotensin Aldosterone Syst     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Albuminuria / complications,  drug therapy,  physiopathology,  urine
Angiotensin Receptor Antagonists / pharmacology,  therapeutic use*
Biopterin / analogs & derivatives,  blood
Blood Pressure / drug effects*
Deoxyguanosine / analogs & derivatives,  urine
Diabetes Mellitus, Type 2 / complications,  drug therapy,  physiopathology,  urine
Diabetic Nephropathies / complications,  drug therapy*,  physiopathology,  urine
Female
Hemodynamics / drug effects
Humans
Kidney / drug effects,  metabolism*,  pathology,  physiopathology
Male
Middle Aged
Nitrates / urine
Nitric Oxide / biosynthesis*
Nitrites / urine
Receptors, Angiotensin / metabolism*
Sodium Chloride, Dietary / pharmacology*
Tetrazoles / pharmacology,  therapeutic use
Valine / analogs & derivatives,  pharmacology,  therapeutic use
Chemical
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Nitrates; 0/Nitrites; 0/Receptors, Angiotensin; 0/Sodium Chloride, Dietary; 0/Tetrazoles; 137862-53-4/valsartan; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 31C4KY9ESH/Nitric Oxide; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; G9481N71RO/Deoxyguanosine; HG18B9YRS7/Valine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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