Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/ day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase.

Original languageEnglish (US)
Pages (from-to)567-575
Number of pages9
JournalMicrocirculation
Volume13
Issue number7
DOIs
StatePublished - Oct 1 2006

Fingerprint

NADPH Oxidase
Arterioles
Type 1 Diabetes Mellitus
Nitric Oxide Synthase
Parietal Lobe
Superoxides
Microvessels
Cerebral Cortex
Adenosine Diphosphate
Acetylcholine
Nitroglycerin
Protein Subunits
Streptozocin
Vasodilation
Drinking Water
Dilatation
Western Blotting
acetovanillone
Proteins

Keywords

  • Acetylcholine
  • Adenosine diphosphate
  • Apocynin
  • Brain
  • Nitric oxide
  • Nitroglycerin
  • Rats
  • Type I diabetes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus. / Mayhan, William G.; Arrick, Denise M.; Sharpe, Glenda M.; Patel, Kaushik P.; Sun, Hong.

In: Microcirculation, Vol. 13, No. 7, 01.10.2006, p. 567-575.

Research output: Contribution to journalArticle

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abstract = "Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/ day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase.",
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T1 - Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus

AU - Mayhan, William G.

AU - Arrick, Denise M.

AU - Sharpe, Glenda M.

AU - Patel, Kaushik P.

AU - Sun, Hong

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AB - Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/ day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase.

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KW - Adenosine diphosphate

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KW - Rats

KW - Type I diabetes

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