nNOS-dependent reactivity of cerebral arterioles in Type 1 diabetes

Denise M. Arrick, Glenda M. Sharpe, Hong Sun, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Our goals were to determine whether Type 1 diabetes (T1D) alters neuronal nitric oxide synthase (nNOS)-dependent reactivity of cerebral arterioles and to identify a potential role for oxidative stress in T1D-induced impairment in nNOS-dependent responses of cerebral arterioles. Rats were injected with vehicle (sodium citrate buffer) or streptozotocin (50 mg/kg IP) to induce T1D. Two to three months later, we measured functional responses of cerebral arterioles to nNOS-dependent (NMDA and kainate) and -independent (nitroglycerin) agonists in nondiabetic and diabetic rats before and during inhibition of oxidative stress using tempol (100 μM). In addition, we measured superoxide anion production under basal conditions, during stimulation with NMDA and kainate, and during treatment with tempol. We found that nNOS-dependent, but -independent, vasodilatation was impaired in diabetic compared to nondiabetic rats. In addition, treatment of the cerebral microcirculation with tempol restored impaired nNOS-dependent vasodilatation in diabetic rats toward that observed in nondiabetic rats. Furthermore, the production of superoxide anion (lucigenin chemiluminescence) was increased in parietal cortical tissue of diabetic rats under basal conditions. Application of NMDA and kainate did not increase superoxide anion production in nondiabetic or diabetic rats. However, tempol decreased basal production of superoxide anion in diabetic rats. Our findings suggest that T1D impairs nNOS-dependent dilatation of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide anion.

Original languageEnglish (US)
Pages (from-to)365-371
Number of pages7
JournalBrain Research
Issue number1
StatePublished - Dec 12 2007


  • Brain
  • Diabetes
  • Kainate
  • NMDA
  • Nitric oxide
  • Superoxide anion

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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