Abstract 15410: ACE Gene Dosage Influences the Magnitude of Blood Pressure Increase After Chronic High Fructose Intake: Role of Resistance Arteries
We investigated the mechanisms involved in blood pressure (BP) increase induced by chronic high fructose (F) intake and its association with angiotensin converting enzyme (ACE) dosage.
Male mice harbouring 1, 2 or 3 copies of the ACE gene received F (100g/l) or tap water (C) for 8 weeks. Glucose tolerance and BP were evaluated. BP variability was analyzed in frequency domain. Mesenteric resistance artery reactivity to noradrenaline (Nor; 0.1nM - 1μM), and acetylcholine (Ach; 1nM - 10μM, after or not L-NAME incubation, 100 μM) were studied in an isometric myograph (DMT, 620M).
Glucose intolerance was seen in all F groups vs. C (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 at the 120thmin after 1.5 g/Kg ip glucose overload). Systolic BP increased in all F-fed mice (mean C=112+2; F:1 copy=119+3, 2 copies=123+2, 3 copies=129+2 mmHg), with a significant augment in 3-copy group vs. 1 and 2-copy mice. Not only BP variability (1 copy: 39+3 vs. F=57+2; 2 copies: 38+2 vs. F=59+3; 3 copies: 40+3 vs. F=73+7 mmHg2) but also its sympathetic component (LF; 1 copy: 5+1 vs. F=12+3; 2 copies: 6+2 vs. F=19+3; 3 copies: 7+2 vs. F=31+5 %) increased in all F groups, with a more pronounced augment in 3-copy mice vs. 1 and 2. Moreover, F-fed 3-copy mice reactivity to Nor was superior than the other groups (1 copy: 170+5; 2 copies: 190+7; 3 copies: 214+10 %) while Ach-induced relaxation was more reduced in 3-copy mice than 1 and 2 (mean C: 76+5%; F: 1 copy=58+8, 2 copies=47+6, 3 copies=36+5 %). L-NAME in F-fed groups significantly blocked ~95% of Ach relaxation in 3-copy mice vs. 75 and 82% in 1 and 2-copy mice, respectively. Additionally, BP variability was negatively correlated to Ach maximal relaxation (r2=0.75) and positively correlated to Nor maximal constriction (r2=0.78) while glucose levels in the tolerance test were also negatively correlated to Ach maximal relaxation (r2=0.72) and positively correlated to Nor maximal constriction (r2=0.9).
In conclusion, F-induced BP increase is influenced by ACE levels in mice. Increased BP variability and glucose intolerance are highly associated with microvascular dysfunction.
Author Disclosures: I.C. Moraes-Silva: None. L.E. de Souza: None. M. Irigoyen: None. D.E. Casarini: None.
- © 2015 by American Heart Association, Inc.