title: Low-dose enalapril reduces angiotensin II and attenuates diabetic-induced cardiac and autonomic dysfunctions.
abstract: Activation of renin-angiotensin system has been linked to cardiovascular and autonomic dysfunctions in diabetes. Experiments were performed to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI), enalapril, on cardiac and autonomic functions in diabetic rats. Diabetes was induced by streptozotocin (50 mg/kg), and rats were treated with enalapril (1 mg · kg(-1) · d(-1)). After 30 days, evaluations were performed in control, diabetic, and enalapril-treated groups. Cardiac function was evaluated by echocardiography and through cannulation of the left ventricle (at baseline and in response to volume overload). Heart rate and systolic blood pressure variabilities were evaluated in the time and frequency domains. Streptozotocin rats had left ventricular systolic and diastolic dysfunctions, expressed by reduced ejection fraction and increased isovolumic relaxation time. The ACEI prevented these changes, improved diastolic cardiac responses to volume overload and total power of heart rate variability, reduced the ACE1 activity and protein expression and cardiac angiotensin (Ang) II levels, and increased angiotensin-converting enzyme 2 activity, despite unchanged blood pressure. Correlations were obtained between Ang II content with systolic and diastolic functions and heart rate variability. These findings provide evidence that the low-dose ACEI prevents autonomic and cardiac dysfunctions induced by diabetes without changing blood pressure and associated with reduced cardiac Ang II and increased angiotensin-converting enzyme 2 activity.
authors.affiliation: Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Malfitano
authors.forename: Kátia
authors.initials: K
authors.lastname: De Angelis
authors.forename: Tiago
authors.initials: T
authors.lastname: Fernandes
authors.forename: Rogério Brandão
authors.initials: RB
authors.lastname: Wichi
authors.forename: Kaleizu
authors.initials: K
authors.lastname: Rosa
authors.forename: Mariana
authors.initials: M
authors.lastname: Pazzine
authors.forename: Cristiano
authors.initials: C
authors.lastname: Mostarda
authors.forename: Fernanda Aparecida
authors.initials: FA
authors.lastname: Ronchi
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: Oliveira
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: de Oliveira
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
authors.forename: Maria-Claudia
authors.initials: MC
authors.lastname: Irigoyen
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D000804:Angiotensin II; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2