Abstract 194: Low Levels of Angiotensin Converting Enzyme (ace) Do Not Prevent From Metabolic Alterations And Endothelial Dysfunction of Resistance Arteries Induced by High Fructose Intake
Purpose: ACE gene polymorphism may be associated with different responses to cardiovascular and metabolic disturbances. Therefore, we tested whether mice with low vs. normal levels of circulating and tissue ACE differently responds to chronic and excessive fructose (F) consumption.
Methods: Male mice (22±1g) harboring 1 or 2 copies of the ACE gene received F (100mg/l) or tap water for 8 weeks. Blood pressure (BP) was measured by plethysmography. Glycemia, lipids and glucose tolerance (0 to 120 min after glucose load=1.5 g/Kg ip) were also evaluated. After euthanasia, the white adipose tissue was weighed and the mesenteric resistance artery (MRA) was dissected out. Relaxation of MRA rings was evaluated in an isometric myograph in response to acetylcholine (Ach;0.01nM-30μM) or sodium nitroprusside (SNP; 0.01nM-300μM) after pre-constriction with noradrenaline.
Results: Caloric intake (~ 12.7 kcal/day) and body weight gain (1 copy: ~40%; 2 copies: ~30%) were similar among all groups. However, adipose tissue deposition was 43% higher in 1-copy F-fed mice and 36% higher in 2-copy F-fed mice in relation to the controls (p<0.05), with no influence of ACE gene copy number. F consumption increased systolic BP in 2-copy mice (1 copy: 114±2 vs. F=116±2; 2 copies: 113±2 vs. F=122±1 mmHg) while diastolic BP was increased in both F-fed groups (1 copy: 79±1 vs. F= 88±2; 2 copies: 81±2 vs. F=93±2 mmHg). This augment in BP was significantly higher in 2-copy than in 1-copy mice (p<0.05). F-fed mice also presented hyperglycemia (1 copy: 84±3 vs. F=128±5; 2 copies: 85±4 vs. F=133±8 mg/dl) as well as glucose intolerance (increase of ~67% in the area under time course curve); with no alterations in total cholesterol nor triglycerides. MRA % of relaxation was unaltered in response to SNP, while F-fed groups showed reduced relaxation response to Ach (1 copy: 87% vs. F=51%; 2 copies: 92% vs. F=57%).
Conclusions: F intake provokes glucose intolerance, increases visceral adipose tissue deposition and decreases endothelium-dependent relaxation of resistance arteries at a similar magnitude for both, 1- and 2-copy ACE gene mice, while F-induced BP increase seems to be more dependent on ACE gene dosage.
- © 2013 by American Heart Association, Inc.