Vascular reactivity in the Butterball mouse, a new model of early onset obesity and hyperglycemia, is altered in a sex‐dependent manner

Obesity complicated by metabolic syndrome has emerged recently as an epidemic in Western cultures. Chronic obesity and type II diabetes, elements of metabolic syndrome, are risk factors for cardiovascular disease. Using a mouse that spontaneously developed an obese phenotype (Butterball, BB) we set out to probe the vascular response characteristics at 27 weeks of age. Thoracic aortas from either male or female Lean (L) and BB mice were isolated and cumulative dose‐response relationships were constructed using phenylephrine (PE) and acetylcholine (ACH) to probe their vascular responses. Maximal PE contractions were different between the L female (0.8 ± 0.2 mN/mm 2 ) and female BB (1.6 ± 0.2* mN/mm 2 *) or L and BB males (1.3 ± 0.2 mN/mm 2 *and 1.7 ± 0.3 mN/mm 2 *). The sensitivity to PE also was different in the females (EC 50 L = 0.57 ± 0.10; BB = 0.31 ± 0.08 μM*) and shifted left relative to the males (EC 50 L = 0.84 ± 0.12; BB = 0.58 ± 0.13 μM). The endothelial‐dependent relaxations showed both a significant reduction in % relaxation (L = 103 ± 8 and BB = 45 ± 10*) and sensitivity (EC 50 L = 0.05 ± 0.02; BB = 0.43 ± 0.10 μM*) to ACH in female BB mice, but only a decreased sensitivity was seen in males (EC 50 L = 0.09 ± 0.02; BB = 0.20 ± 0.06 μM*). The results demonstrate an altered endothelial‐dependent and independent vascular responsiveness that is sex‐dependent in these obese mice.