Abstract 19: Chronic Infusion of Angiotensin-(1-7) into the Lateral Ventricle of the Brain Improves Cardiovascular and Metabolic Parameters in Fructose-Fed Rats

Abstract

We evaluated whether chronic intracerebroventricular (ICV) infusion of angiotensin (Ang)-(1-7) improves cardiovascular and metabolic parameters in fructose-fed rats. Six-weeks-old Sprague-Dawley rats were fed with either normal rat chow (CTL, n=11-13) or the same diet plus 10% fructose in drinking water (FRUT, n=7-10) for 10 wks. On the 6^th wk of fructose diet, a set of rats were subjected to ICV infusion of Ang-(1-7) (FRUT-A7; 200 ng/ hour; n=7-9) for 28 days. Baseline mean arterial pressure (MAP), cardiac baroreflex sensitivity (BRS, phenylephrine bolus iv), and the cardiac autonomic tone (pharmacological blockade of β-adrenergic and muscarinic receptors) were evaluated. Another group of rats were subjected to glucose tolerance test (2 g/kg rat, 50% solution ip) and extraction of blood and tissues after 6-8 h fasting. Compared to CTL, FRUT had reduced BRS (0.53 ± 0.05 vs 0.96 ± 0.08 ms/mmHg), with no changes in MAP, and cardiac autonomic tone. Moreover, FRUT displayed hyperglycemia (142 ± 2 vs 128 ± 3 mg/ dL), hyperinsulinemia (1.8 ± 0.1 vs 1.3 ± 0.1 ng/ ml), hyperleptinemia (5 ± 0.2 vs 3 ± 0.5 ng/ ml), and hypertriglyceridemia (106 ± 13 vs 79 ± 5 mg/ dL). These changes were followed by impaired response to tolerance glucose test (258 ± 19 vs 177 ± 39 mg/ dL), sustained for 60 min, and liver hypertrophy (33 ± 1 vs 29 ± 0.5 mg/ g body weight) with lower hepatic glycogen levels (9 ± 2 vs 15 ± 1 mg/ g liver). In contrast, FRUT-A7 rats had normalized BRS (0.96 ± 0.07 ms/ mmHg), reduced cardiac sympathetic tone (20% change vs CTL and FRUT), with no change in parasympathetic tone or MAP. Similar to FRUT, FRUT-A7 showed hypertriglyceridemia (115 ± 9 mg/ dL), and hyperleptinemia (5 ± 0.4 ng/ ml). However, serum insulin (1.4 ± 0.1 ng/ ml) and glucose (129 ± 4 mg/ dl), response to tolerance glucose test (178 ± 41 mg/ dL), liver relative weight (30 ± 0.7 mg/ g) and glycogen deposition (14 ± 1.8 mg/ g) were normalized in these rats. Total cholestherol (∼10%) and high density lipoprotein (∼20%) were increased in FRUT-A7 (p<0.05). There was no change in glucagonemia, body weight gain, or relative weight of left ventricle, and adipose tissues among all groups. These data showed that chronic ICV infusion of Ang-(1-7) produced important benefits on cardiovascular and metabolic parameters in fructose-fed rats.