Abstract 19589: ACE Gene Dosage Impairs Cardiovascular Autonomic Dysfunction in Diabetic Animals

Clinical studies showed that the ACE I/D genotypes are not associated with the systolic or diastolic blood pressure. However, some studies have showed that high concentrations of ACE are deleterious to the kidney in a hyperglycemic environment. The aim of this study was assess hemodynamics and cardiovascular autonomic changes as well as the expression of renal angiotensin II in mice with 2 and 3 ACE gene copies, with or without diabetes streptozotocin , 50 mg/kg, IV; STZ). STZ induced diabetic were ACE2D (n= 10) and ACE3D (n=10). Systolic, diastolic, mean arterial pressure and heart rate were evaluated. Heart rate variability and renal angiotensin II were quantified. The data have shown a reduction in heart rate in diabetic animals compared to controls (ACE2=611 ± 14; ACE3596 ± 25; ACE2D347 ± 34; ACE3D317 ± 62bpm) and, as expected, blood glucose was higher in diabetic groups (ACE2=99 ± 7; ACE397 ± 2; ACE2D467 ± 23; ACE3D513 ± 12 mg/dl). Although the variance of pulse interval was not different among the groups (ACE2D= 22,83 ± 4,51; ACE3D = 41,40 ± 13,31; ACE2= 38,50 ± 8,54; ACE3= 29,63 ± 4,76 ms), ACE3D group showed increased sympathetic modulation (LF%ACE3D= 60,78 ± 6,55; ACE2D= 33,25 ± 3,71; ACE2= 31,55 ± 4,07; ACE 3= 33,54 ± 7,0) and lower vagal modulation (HF%ACE3D= 39,22 ± 6,55; ACE2D= 66,75 ± 3,71; ACE2= 68,45 ± 4,07; ACE3= 66,46 ± 7,00) than controls which resulted in an increased sympathovagal balance in the heart (LF/HFACE3D= 2,20 ± 0,68; ACE2D= 0,54 ± 0,10; ACE2= 0,48 ± 0,08; ACE 3= 0,57 ± 0,16) compared to the other groups. Moreover, Angiotensin II in the renal cortex was higher in ACE3D group compared to other groups (ACE3D= 1,70 ± 0,14; ACE2D= 0,97 ± 0,10; ACE2= 0,15 ± 0,03; ACE 3= 1,02 ± 0,22cel/mm). A small increase in ACE levels induced by genetic manipulation in diabetic mice promoted autonomic injury. The development of cardiovascular autonomic changes in diabetes may be exacerbated by activation of the RAS.