Effect of combination therapy with dipyridamole and quinapril in diabetic nephropathy

Autor: Toshiro Fujita, Atsuo Goto, Akihiro Tojo, Maristela L. Onozato
Rok vydání: 2003
Předmět:
Blood Glucose
Lipid Peroxides
medicine.medical_specialty
Combination therapy
Phosphodiesterase Inhibitors
Endocrinology
Diabetes and Metabolism
Blotting
Western
Renal function
Angiotensin-Converting Enzyme Inhibitors
Nitric Oxide Synthase Type I
Kidney
Diabetes Mellitus
Experimental
Rats
Sprague-Dawley
Diabetic nephropathy
Random Allocation
chemistry.chemical_compound
Endocrinology
Tetrahydroisoquinolines
Internal medicine
Internal Medicine
medicine
Albuminuria
Animals
Diabetic Nephropathies
NADH
NADPH Oxidoreductases
Cyclic GMP
Creatinine
business.industry
Quinapril
NADPH Oxidases
Dipyridamole
General Medicine
Isoquinolines
Phosphoproteins
medicine.disease
Immunohistochemistry
Rats
chemistry
NAD(P)H oxidase
ACE inhibitor
Drug Therapy
Combination
Female
Nitric Oxide Synthase
business
medicine.drug
Zdroj: Diabetes Research and Clinical Practice. 59:83-92
ISSN: 0168-8227
DOI: 10.1016/s0168-8227(02)00154-7
Popis: Background/aims: Dipyridamole stimulates nitric oxide action via inhibition of phosphodiesterase and also has an antioxidant effect. ACE inhibitor reduces glomerular pressure and enhances NO action via increased bradykinin. Thus, we evaluated the effect of the combination of dipyridamole and ACE inhibitor in diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats at 2 weeks were treated with dipyridamole, quinapril or both. The expression of NOS and NAD(P)H oxidase p47phox was investigated using immunohistochemistry and western blot, and urinary albumin, cGMP and lipid peroxidation products (LPO) were measured at 4 weeks. Results: NAD(P)H oxidase and urinary LPO were significantly enhanced in diabetes, and suppressed by each treatment to the same extent. The nNOS expression in macula densa and eNOS increased significantly with combination therapy compared to quinapril treatment alone contributing to an enhanced urinary excretion of cGMP and to maintain the creatinine clearance. Increased albuminuria in diabetes was reduced more effectively with combination therapy to the control level than with single treatments. Conclusion: Combination therapy with dipyridamole and quinapril suppressed urinary LPO via reduction of NAD(P)H oxidase increase in diabetes. The combination therapy reduced microalbuminuria to the control level and maintained creatinine clearance with enhanced nNOS and eNOS expression compared to quinapril alone.
Databáze: OpenAIRE
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