title: Effects of captopril on cardiovascular reflexes and respiratory mechanisms in rats submitted to monocrotaline-induced pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary Arterial Hypertension (PAH) is a disease associated with increased arteriolar resistance in the lungs. Due to hypoxemia, some physiological mechanisms can be posteriorly affected, including respiratory and cardiovascular reflexes, but this has not yet been fully investigated. This study aimed to evaluate how these mechanisms were affected by monocrotaline (MCT)-induced PAH and the possible therapeutic role of angiotensin converting enzyme inhibitor (ACEi), captopril, in reversing this remodeling process.
  
  
  RESULTS
  Groups of Wistar rats received MCT injections (60 mg kg(-1)). Three weeks later, they received captopril (CPT, 100 mg kg(-1)) in their drinking water (MCT + CPT) or water alone (MCT) for 2 weeks. As control, saline-treated animals received captopril in their drinking water (CPT) or water alone (CON), also for 2 weeks. Results showed that PAH was fully induced in the MCT group, evidenced by a high pulmonary index. Gasometrical and respiratory analyses showed hypoxemia and compensatory hyperventilation. CPT treatment brought these parameters to similar values to those observed in the CON group. We observed that autonomic dysfunction in the MCT group was suppressed by CPT. Finally, cardiovascular reflexes analysis showed increased chemoreflex responses in the MCT group, while baroreflex sensibility was decreased. Surprisingly, CPT normalized these reflex responses to values similar to the CON group.
  
  
  CONCLUSIONS
  The present study demonstrates that MCT-induced PAH induces compensatory respiratory responses, dysautonomia, and baroreflex dysfunction and increases chemoreflex responses. The data also indicate that CPT was effective in reversing these cardio-respiratory disorders, suggesting that ACEi could be a potential therapeutic target for PAH.
authors.affiliation: Department of Integrated Health Education, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil; Department of Physiological Sciences, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Verônica Lourenço
authors.initials: VL
authors.lastname: Wittmer
authors.affiliation: Department of Physiological Sciences, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Élio Junior
authors.initials: ÉJ
authors.lastname: Waichert
authors.affiliation: Department of Integrated Health Education, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil; Department of Physiological Sciences, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Pablo Lúcio
authors.initials: PL
authors.lastname: Gava
authors.affiliation: Pathology, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Fausto Edmundo Lima
authors.initials: FE
authors.lastname: Pereira
authors.affiliation: Department of Morphology, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Marco Cesar Cunegundes
authors.initials: MC
authors.lastname: Guimarães
authors.affiliation: Department of Physiological Sciences, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Suely Gomes
authors.initials: SG
authors.lastname: de Figueiredo
authors.affiliation: Department of Physiological Sciences, Center of Health Science, Federal University of Espírito Santo, Vitória, ES, Brazil. Electronic address: hmauad@terra.com.br.
authors.forename: Hélder
authors.initials: H
authors.lastname: Mauad
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016686:Monocrotaline; D002216:Captopril
keywords: Baroreflex; Captopril; Chemoreflex; Monocrotaline; Pulmonary Arterial Hypertension