title: Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats.
abstract: OBJECTIVE
  Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats.
  
  
  RESULTS
  We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet.
  
  
  CONCLUSIONS
  Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.
authors.affiliation: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Silvio Rodrigues
authors.initials: SR
authors.lastname: Marques-Neto
authors.affiliation: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Castiglione
authors.affiliation: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Aiza
authors.initials: A
authors.lastname: Pontes
authors.affiliation: Cardiac Electrophysiology Laboratory, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Dahienne Ferreira
authors.initials: DF
authors.lastname: Oliveira
authors.affiliation: Cardiac Electrophysiology Laboratory, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Emanuelle Baptista
authors.initials: EB
authors.lastname: Ferraz
authors.affiliation: Cardiac Electrophysiology Laboratory, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: José Hamilton Matheus
authors.initials: JH
authors.lastname: Nascimento
authors.affiliation: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Eliete
authors.initials: E
authors.lastname: Bouskela
mesh_terms: D000818:Animals; D001699:Biometry; D002319:Cardiovascular System / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D059305:Diet, High-Fat; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D054795:Incretins / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008933:Mitochondrial Swelling / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects*; D017208:Rats, Wistar
chemical_list: D054795:Incretins; D005947:Glucose
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