Abstract 315: Endothelial And Autonomic Dysfunctions Induced By High Fructose Intake Are Modulated By The Angiotensin Converting Enzyme (ACE) Gene Dosage

Abstract

ACE gene polymorphism may be associated with different responses to physiological and pathological stimuli. Therefore, we tested whether low, normal or high levels of ACE gene dosage influence on the effects of chronic and excessive fructose intake (F). Male mice (22±1g) harboring 1, 2 or 3 copies of the ACE gene received F (100g/l) or tap water for 8 weeks. After this period, glucose tolerance (0-120 min after glucose load=1.5 g/Kg ip) and lipids were measured; blood pressure (BP) signals were recorded (Windaq, 4kHz), and BP variability was analyzed in frequency domain (FFT). After euthanasia, mesenteric resistance artery (MRA) was dissected out and rings were mounted in an isometric myograph (DMT,620M). MRA responses to noradrenaline (Nor; 0.1nM-1μM) and acetylcholine (Ach; 0.01nM-30μM) were studied. One-way ANOVA and p<0.05 were used for statistical analysis F induced glucose intolerance (1 copy: 100±3 vs. F=198±5; 2 copies: 121±4 vs. F=201±8; 3 copies: 86±4 vs. F=212±5 mg/dl after 120 min) with no alterations in total cholesterol nor triglycerides. Systolic BP increased in 2 and 3-copy mice after F (1 copy: 119±2 vs. F=124±4; 2 copies: 120±3 vs. F=131±3; 3 copies: 121±3 vs. F=139±4 mmHg) and diastolic BP increased in all F-fed groups (1 copy: 80±2 vs. F=92±3; 2 copies: 83±2 vs. F=95±4; 3 copies: 84±2 vs. F=100±2 mmHg). The augment in systolic BP was significantly higher in 3-copy (17±1 mmHg) vs. 1 (6±1 mmHg) and 2-copy mice (10±1 mmHg). F also increased BP variability in all groups, with a more pronounced augment in 3-copy mice vs. other groups (1 copy: 39±3 vs. F=57±2; 2 copies: 37±2 vs. F=60±3; 3 copies: 40±3 vs. F=73±7 mmHg 2 ). Additionally, the sympathetic component of BP variability (LF %) presented a similar behavior (1 copy: 5±1 vs. F=12±3; 2 copies: 6±2 vs. F=19±3; 3 copies: 7±3 vs. F=31±5 %). Ach-induced relaxation was reduced in F mice (1 copy: 78 vs. F=58; 2 copies: 76 vs. F=47; 3 copies: 73 vs. F=36 %) and a hyperreactivity to Nor was also observed (1 copy: 92 vs. F=170; 2 copies: 107 vs. F=190; 3 copies: 101 vs. F=214 %). In both responses, 3-copy mice were significantly different than the other groups. ACE gene dosage seems to modulate the magnitude of MRA and autonomic dysfunctions caused by F consumption, inducing a more increased cardiovascular risk for 3-copy mice.