Effect of High-Fat Diet on the Regulation of Vascular Tone in Arteries of Young Mice

Abstract

The prevalence of overweight and obesity is increasing in all age groups and continents. The leading cause is nutritional intake of high amounts of fat. Obesity is a major risk factor for endocrine and cardiovascular diseases like high blood pressure, insulin resistance and the subsequent development of atherosclerosis. Childhood obesity affects cardiac function instantly and is a risk factor for coronary heart disease and unfavorable metabolic changes in adulthood, independent from body weight at that time. The objective of this study was to investigate changes in vascular reactivity of the aorta and carotid arteries of young mice in response to high dietary fat intake. 4 weeks old C57BL/6J mice were either fed a high-fat diet (Obese group) or standard rodent chow (Control group) for 30 weeks. Vascular responses to phenylephrine (PE) and acetylcholine (ACh) were investigated in aortic and carotid artery rings of these animals ex vivo, in absence and presence of nitric oxide (NO) and endoperoxides. Compared to the Control group, the mice of the Obese group showed glucose intolerance, greater weight gain and altered responses to vasoactive agents. The contractile response to PE was enhanced and was further augmented by inhibition of NO production in the aorta of the Obese group, whereas in the carotid artery of the Obese group and in the Control group the contraction remained unaffected. Relaxations to ACh were not diminished in the Obese group. In untreated vessels, contractions to high concentrations of ACh were observed in the carotid artery. They were abolished by an unspecific cyclooxygenase-inhibitor. Inhibition of endogenous NO production abrogated endothelium-dependent relaxations to ACh and contractile responses were observed in all vessels. These endothelium-dependent contractions were stronger and started at lower concentrations in the carotid artery and were increased by obesity. In conclusion, the findings of the present study suggest that a high dietary fat intake leads to weight gain, glucose intolerance and enhanced vascular contractile response in adolescent mice. The heterogenous diet-induced changes indicate selective effects on different vascular beds. These findings may be important to understand the variability in the onset and progression of vascular diseases in different vascular beds in obese patients and to develop efficient therapeutic strategies.