Abnormal vascular reactivity in experimental diet-induced diabetes (C57BL/6J mice)

When fed a high-fat, high-carbohydrate diet (HFC), C57BL/6J mice become obese and hypertensive, and exhibits several of the metabolic disturbances associated with non-insulin dependent (type II) diabetes: elevated glucose and insulin levels and dyslipidemia. However, the functional properties of their arteries have not been characterized Therefore, we studied the reactivity of small arteries isolated from HFC-fed (18 weeks) C57BL/6J mice by comparison with arteries isolated from normal-chow fed (NFC) animals (n=12/group). Non-susceptible mice (A/J) mice were also studied in order to determine the interaction between diet and strain. Arteries were mounted in a wire myograph and the response to norepinephrine (NE), serotonin (5-HT), acetylcholine (Ach) and Na nitroprusside (SNP) determined. The data show that HFC diet decreased significantly Ach-dependent relaxation (p<0.02, ANOVA, interaction with strain = NS, Figure) but did not affect that to NE, 5-HT and SNP. In contrast Ach-induced contractions were higher in the diabetic strain (*,p<0.05; Fig.). Measurement of free [Ca²⁺] in fura-2 loaded arteries further showed that basal _i[Ca²⁺] was higher (p<0.05) in BL/6 mice than in A/J controls. In contrast, the _i[Ca²⁺] responses to KCl and NE were significantly (p<0.02;p<0.050) decreased by the HFC diet but similar in both strains. We conclude from the study that abnormal vascular reactivity in type-II diabetes is the consequence of combined genetic and diet-induced factors. (Figure Presented).