Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

Abstract

We evaluated effects of chronic intracerebroventricular infusion of angiotensin (Ang)-(1–7) on cardiovascular and metabolic parameters in fructose-fed (FF) rats. After 6 weeks of fructose intake (10% in drinking water), Sprague-Dawley rats were subjected to intracerebroventricular infusion of Ang-(1–7) (200 ng/h; FF+A7 group) or 0.9% sterile saline (FF group) for 4 weeks with continued access to fructose. Compared with control rats, FF rats had increased mean arterial pressure and cardiac sympathetic tone with impaired baroreflex sensitivity. FF rats also presented increased circulating triglycerides, leptin, insulin, and glucose with impaired glucose tolerance. Furthermore, relative weights of liver and retroperitoneal adipose tissue were increased in FF rats. Glycogen content was reduced in liver, but increased in muscle. In contrast, fructose-fed rats subjected to chronic intracerebroventricular infusion of Ang-(1–7) presented reduced cardiac sympathetic tone with normalized mean arterial pressure, baroreflex sensitivity, glucose and insulin levels, and improved glucose tolerance. Relative weight of liver, and hepatic and muscle glycogen contents were also normalized in FF+A7 rats. In addition, FF+A7 rats had reduced mRNA expression for neuronal nitric oxide synthase and NR1 subunit of N -methyl- d -aspartate receptor in hypothalamus and dorsomedial medulla. Ang-(1–7) infusion did not alter fructose-induced hyperleptinemia and increased relative weight of retroperitoneal adipose tissue. There were no differences in body weights, neither in liver mRNA expression of phosphoenolpyruvate carboxykinase or glucose-6-phosphatase among the groups. These data indicate that chronic increase in Ang-(1–7) levels in the brain may have a beneficial role in fructose-fed rats by ameliorating cardiovascular and metabolic disorders.