Female mice are more sensitive to obesity‐induced vascular dysfunction than males (680.14)

Abstract

Over the last two decades, a three fold increased in the prevalence of cardiovascular disease (CVD) has been reported in premenopausal women and attributed to the recent epidemic of obesity. While the mechanisms involved in obesity‐related CVD are beginning to be understood in males they remain unknown and unstudied in females. We tested the hypothesis that obesity negates the protection of women from CVD by submitting 6‐week old male and female Balb/C mice to a control (CD) or a high fat diet (HFD) for 12 weeks. On CD, females were smaller than males, but exhibited higher adiposity, fasted glycemia and leptin levels than males. On HFD, females had a higher food intake (HFDF: 3.1±0.5 vs. HFDM: 2.7±0.2g/day) but displayed lower increases in body weight (HFDF: +15% vs. HFDM: +35%), adiposity (HFDF: +12% vs. HFDM: +190%), glycemia and leptin levels than males, suggesting that female mice have a higher metabolic rate than males. Aortic ring reactivity was studied via wire myography at the end of the diet. Consistent with the human literature, at baseline, females displayed a better endothelial function than males (CDF: 82±3 vs. CDM: 49±3%, p<0.05). However 12 weeks of HFD impaired endothelial function (12% reduction in relaxation) and reduced the contractility of the aortic rings to phenylephrine (‐35%), serotonin (‐14%) and depolarization (‐13%), in female mice only, suggesting that females are more sensitive to obesity‐induced vascular dysfunction than males. While reduction in vascular contractility might initially protect females from hypertension, reduced endothelial function might predispose females to atherosclerosis and further cardiovascular events.Grant Funding Source: 11SDG5060006