Effects of long-term inhibition of neuronal nitric oxide synthase (NOS1) in uninephrectomized diabetic rats

Radko Komers, Jessie N. Lindsley, Terry T. Oyama, Sharon Anderson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic changes in diabetes mellitus (DM). However, the role of NO in the pathophysiology of diabetic nephropathy remains controversial. Renal hemodynamic changes in experimental DM can be acutely normalized by selective inhibition of neuronal NO synthase (nNOS). This observation suggests a nephroprotective potential of nNOS inhibition in DM. To explore this issue we assessed the long-term effects (12 weeks) of selective nNOS inhibition with the specific inhibitor S-methyl-l-thiocitrulline (SMTC) in uninephrectomized control and streptozotocin-diabetic rats. No beneficial effects of SMTC were observed in nondiabetic controls. In contrast, SMTC delayed the development of proteinuria (32 ± 8 vs. 53 ± 9 mg/24 h, week 8, p <0.05) and glomerulosclerosis (GS, 0.30 ± 0.08 vs. 0.57 ± 0.05, p <0.05) in diabetic rats. These effects coincided with early effects of treatment on the glomerular filtration rate, and were associated with lower renal expression of nNOS. Furthermore, SMTC-treated diabetic rats demonstrated reduced weight gain and urinary sodium excretion as compared to vehicle-treated counterparts, despite similar metabolic control and blood pressure. In summary, long-term nNOS inhibition had modest nephroprotective effects in uninephrectomized diabetic rats. These effects may be mediated by renal hemodynamic mechanisms, as well as by lower food (protein) intake.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume11
Issue number2
DOIs
StatePublished - Sep 2004

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Nitric Oxide Synthase Type I
Nitric Oxide Synthase
Rats
Hemodynamics
Medical problems
Kidney
Diabetes Mellitus
Nitric Oxide
Experimental Diabetes Mellitus
Blood pressure
Diabetic Nephropathies
Streptozocin
Glomerular Filtration Rate
Proteinuria
Weight Gain
Eating
Sodium
Blood Pressure
thiocitrulline
Proteins

Keywords

  • Diabetic nephropathy
  • Glomerular filtration rate
  • Glomerulosclerosis
  • Neuronal nitric oxide synthase
  • NOS1
  • Proteinuria

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Effects of long-term inhibition of neuronal nitric oxide synthase (NOS1) in uninephrectomized diabetic rats. / Komers, Radko; Lindsley, Jessie N.; Oyama, Terry T.; Anderson, Sharon.

In: Nitric Oxide - Biology and Chemistry, Vol. 11, No. 2, 09.2004, p. 147-155.

Research output: Contribution to journalArticle

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