Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress

Autor: Yu-Jung Chen, John Quilley, Jing Li
Rok vydání: 2008
Předmět:
Male
Physiology
medicine.medical_treatment
Indomethacin
Kidney
medicine.disease_cause
Antioxidants
chemistry.chemical_compound
Fenofibrate
Hydroxyeicosatetraenoic Acids
Insulin
Enzyme Inhibitors
Arachidonic Acid
biology
Perfusion
Nitric oxide synthase
NG-Nitroarginine Methyl Ester
medicine.anatomical_structure
Enzyme Induction
cardiovascular system
lipids (amino acids
peptides
and proteins)
Arachidonic acid
Cytochrome P-450 CYP4A
Cardiology and Cardiovascular Medicine
medicine.drug
medicine.medical_specialty
Nitric Oxide
Diabetes Mellitus
Experimental
Nitric oxide
Cyclic N-Oxides
Aldehyde Reductase
Physiology (medical)
Internal medicine
Diabetes mellitus
medicine
Animals
Hypoglycemic Agents
Cyclooxygenase Inhibitors
Benzothiazoles
Rats
Wistar
business.industry
Microcirculation
medicine.disease
Streptozotocin
Rats
Oxidative Stress
Endocrinology
chemistry
Prostaglandin-Endoperoxide Synthases
biology.protein
Phthalazines
Tyrosine
Spin Labels
Nitric Oxide Synthase
business
Oxidative stress
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 294:H2305-H2312
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00868.2007
Popis: We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at
Databáze: OpenAIRE
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