Cited by 49Nitric Oxide and Endothelin EffectsCardiovascular Function and Risk FactorsEicosanoids and Hypertension Pharmacology

Diet-induced obesity and diabetes reduce coronary responses to nitric oxide due to reduced bioavailability in isolated mouse hearts

Bender, S. B., Herrick, E. K., Lott, N. D., Klabunde, R. E.·2007·Diabetes Obesity and Metabolism

Abstract

AIM: The aim of the present study was to examine nitric oxide (NO)-mediated coronary vascular responses in a mouse model of obesity and diabetes induced by a high-fat, high-carbohydrate diet. We hypothesized that endogenous NO bioavailability would be reduced in obese/diabetic mouse hearts due to enhanced superoxide anion production, and that coronary smooth muscle responses to exogenous NO would be reduced. METHODS: Age-matched, male C57BL/6J mice were fed either a control diet or a high-fat, high-carbohydrate diet. After 15 weeks, the mice were anesthetized and their hearts were removed and perfused by the Langendorff method under constant flow conditions with an oxygenated buffer solution, and changes in coronary vascular resistance were quantified. RESULTS: Mice fed the high-fat, high-carbohydrate diet became obese, hyperglycaemic and hyperinsulinaemic. Coronary vasoconstrictor responses to NO synthase inhibition by N(omega)-nitro-L-arginine methyl ester were reduced in obese/diabetic mice; normal responses were restored by pretreatment with the superoxide dismutase mimetic 2,2,6,6-tetramethyl-1-piperidinyloxy (Tempol). Coronary endothelium-independent vasodilation to the NO donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) was reduced; however, 8-bromo-cyclic guanosine monophosphate (cGMP)-induced vasodilation was unchanged in obese/diabetic hearts. CONCLUSIONS: These findings suggest that in a diet-induced mouse model of obesity and diabetes, NO bioavailability is reduced by increased superoxide NO scavenging leading to impaired NO-mediated vasodilation. Furthermore, the attenuation of SNAP-induced vasodilation may be due to increased reactive oxygen species scavenging of exogenous NO because normal vascular smooth muscle NO signalling is maintained as indicated by similar 8-bromo-cGMP responses in control and obese/diabetic hearts.

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Crossref · 10.1111/j.1463-1326.2006.00650.x

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  • NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin-resistant patients.

    “NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [116]

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Authors
Bender, S. B., Herrick, E. K., Lott, N. D., & Klabunde, R. E.
Affiliations
Ohio University (US)
Corresponding author
Klabunde, R. E.
Venue
Diabetes Obesity and Metabolism
Publisher
Wiley
Published
2006-09-08
Volume
9
Issue
5
Pages
688-696
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
OpenAlex
W2086586613
Cited by
49
References
45
Citations by year
2025: 1 · 2024: 6 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 2
FWCI
0.44
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
nitric oxide bioavailability, diet-induced obesity, diabetes mellitus, coronary vasodilation, superoxide, oxidative stress, endothelium-independent relaxation, SNAP, cGMP signaling, coronary vascular resistance, high-fat high-carbohydrate diet, nitric oxide synthase inhibition, tempol, reactive oxygen species
MeSH terms
Animals, Biological Availability, Coronary Circulation, Diabetes Mellitus, Dietary Carbohydrates, Heart, Mice, Inbred C57BL, Nitric Oxide, Obesity, Superoxides, Mice

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