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Diabetes‐induced reduction in renal medullary nitric oxide (NO) and oxygen tension (pO 2 ) due to increased hepatic arginine metabolism and oxidative stress
Author(s) -
Palm Fredrik,
Friederich Malou,
Carlsson PerOla,
Hansell Peter,
Teerlink Tom,
Liss Per
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a841-d
Subject(s) - endocrinology , medicine , diabetes mellitus , arginine , oxidative stress , nitric oxide , streptozotocin , arginase , chemistry , renal blood flow , kidney , biochemistry , amino acid
Arginine availability as regulator of NO bioavailability has gained growing interest. We hypothesized that diabetes would induce NO deficiency in the renal medulla, with subsequent reduction in pO 2 , due to arginine limitation for NO production. Medullary NO, pO 2 and blood flow were measured in control and streptozotocin‐induced diabetic rats, with or without α‐tocopherol treatment, during acute iv infusion of L‐arginine followed by L‐NAME. Components of the arginine metabolism were also investigated. Both untreated and tocopherol‐treated diabetic rats had reduced NO compared to controls (59±4, n=10 and 67±7, n=7 vs. 122±7 nmol/l, n=8, respectively). Arginine increased NO in diabetic rats and not in controls, and totally restored NO in tocopherol‐treated animals. Although blood flow increased equally in all groups, arginine selectively increased pO 2 in diabetic rats. Diabetes decreased plasma arginine and ADMA concentrations, but increased hepatic CAT‐2A and ornithine levels independent of tocopherol treatment. In conclusion, diabetic rats had reduced renomedullary NO and pO 2 , which was independent of hemodynamic changes but related to decreased plasma arginine due to increased hepatic arginine metabolism. Reduced oxidative stress augmented the NO response, but did not fully restore NO levels. These changes may be important factors for the development of diabetes‐induced renal dysfunction.