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Effects of a Western diet versus high glucose on endothelium-dependent relaxation in murine micro- and macro-vasculature

Authors :
Ellis, Anthie
Cheng, Zhong-Jian
Li, Yang
Jiang, Yan Fen
Yang, Jing
Pannirselvam, Malarvannan
Ding, Hong
Hollenberg, Morley D.
Triggle, Chris R.
Source :
European Journal of Pharmacology. Dec2008, Vol. 601 Issue 1-3, p111-117. 7p.
Publication Year :
2008

Abstract

Abstract: Vascular contractility and endothelium-dependent vasodilatation were studied in mesenteric, aorta and coronary vasculature from male and female LDL receptor deficient (LDLR-/-) and wild type C57BL/6 mice fed either a high-fat Western Diet (WD) or regular animal chow (RD). Endothelium-dependent vasodilatation was also studied in small mesenteric arteries and aorta from C57BL/6 mice following a 20 h exposure in vitro to 30 mM glucose. Compared with RD-fed animals, WD-fed LDLR-/- animals had increased body weights, elevated triglycerides and total cholesterol, but not glucose. Control C57BL6 animals had elevated body weight without increased cholesterol, triglyceride or glucose levels. The contractile sensitivity to cirazoline (pD2) of small mesenteric arteries was the same for RD-fed LDLR-/- and RD-fed C57BL6 mice, but was reduced in WD-fed male LDLR-/- and WD-fed female C57BL/6 mice. Maximum mesenteric contractile values for cirazoline (Emax) were unchanged; however, the Emax for phenylephrine in the aorta from WD-fed male C57BL/6 (but not LDLR-/- or female C57BL/6) mice was reduced. The Emax for acetylcholine-mediated endothelium-dependent vasodilatation in micro- and macro vessels (small mesenteric artery, coronary artery and aorta) from WD-fed LDLR-/- and C57BL/6 mice was unaltered, in contrast to the reduction in Emax for glucose-exposed tissues. Furthermore, the component of acetylcholine-mediated vasodilatation resistant to the combination of inhibitors of nitric oxide synthase, cyclooxygenase and guanylyl cyclase (nitro L-arginine methyl ester – 100 µM; indomethacin 10 µM and 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one, ODQ – 10 µM, respectively) was generally greater in WD-fed mice. Thus, vasculature from WD-fed mice with short-term dyslipidaemia do not exhibit reduced endothelium-dependent vasodilatation, but the WD is associated with changes in the overall endothelial-dependent relaxation and contractile responses thus suggesting an impact of diet rather than dyslipidaemia on cellular signalling pathways in vascular tissue. In contrast, acute hyperglycaemia resulted in endothelial dysfunction in both small mesenteric arteries and thoracic aorta. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00142999
Volume :
601
Issue :
1-3
Database :
Academic Search Index
Journal :
European Journal of Pharmacology
Publication Type :
Academic Journal
Accession number :
35561108
Full Text :
https://doi.org/10.1016/j.ejphar.2008.10.042