Vascular dysfunction in type 2 diabetic TallyHo mice: Role for an increase in the contribution of PGH2/TxA2 receptor activation and cytochrome p450 products

Cheng, Z, Jiang, Y, Severson, D, Ding, H and Triggle, C 2007, 'Vascular dysfunction in type 2 diabetic TallyHo mice: Role for an increase in the contribution of PGH2/TxA2 receptor activation and cytochrome p450 products', Canadian Journal of Physiology and Pharmacology, vol. 85, no. 34, pp. 404-412.


Document type: Journal Article
Collection: Journal Articles

Title Vascular dysfunction in type 2 diabetic TallyHo mice: Role for an increase in the contribution of PGH2/TxA2 receptor activation and cytochrome p450 products
Author(s) Cheng, Z
Jiang, Y
Severson, D
Ding, H
Triggle, C
Year 2007
Journal name Canadian Journal of Physiology and Pharmacology
Volume number 85
Issue number 34
Start page 404
End page 412
Total pages 9
Publisher National Research Council Canada
Abstract In this study, we tested the hypothesis that spontaneously diabetic TallyHo (TH) mice, a novel polygenic model for type 2 diabetes, will exhibit endothelial dysfunction associated with an increased contribution from endothelium-derived contractile factors (EDCF). The cellular mechanisms underlying the increased contribution of EDCF were explored in 16 and 30-week-old male TH and age-matched male C57BL/6J mice (n = 4-9). Blood glucose and serum lipid profiles were markedly increased in the TH mice. Superoxide generation, assessed with a lucigenin chemiluminescence assay, was markedly increased in the aortae of TH mice. Endothelium-dependent vascular relaxations and contractions to acetylcholine (ACh), but not endothelium-independent relaxations to sodium nitroprusside, were impaired and vascular contractions to phenylephrine were significantly enhanced in aortae from TH mice. N-omega-nitro-L-arginine methyl ester markedly increased the ACh-induced contractions in TH mice, whereas SQ29548, a thromboxane receptor antagonist, and cytochrome P450 (CYP) inhibitors 17-octadecynoic acid and sulfaphenazole, the latter being specific for CYP2C6 and 2C9, decreased and (or) normalized the contractile response to ACh in TH mice. The present study indicates that enhanced contribution of prostaglandin H-2/thromboxane A(2) receptor and CYP, likely CYP2C6 and 2C9, play a critical role in the pathogenesis of increased EDCF in the aortae of type 2 diabetic TH mice.
Subject Basic Pharmacology
Keyword(s) Endothelium-Dependent Contractions
Small Mesenteric-Arteries
Goto-Kakizaki Rats
Hyperpolarizing Factor
Normotensive Rats
Rabbit Aorta
Mouse Model
Inhibition
Vasoconstriction
Acetylcholine
Copyright notice © 2007 NRC Canada
ISSN 0008-4212
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