title: Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice.
abstract: In vitroandex vivoexperiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2in vivois unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice.
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São PauloRibeirão Preto, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São PauloRibeirão Preto, Brazil; Department of Cardiovascular Diseases, Mayo ClinicRochester, MN, USA.
authors.forename: Christiane
authors.initials: C
authors.lastname: Becari
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São PauloRibeirão Preto, Brazil; Department of Medicine, University of Ribeirão PretoRibeirão Preto, Brazil.
authors.forename: Marina T
authors.initials: MT
authors.lastname: Durand
authors.affiliation: Max Delbruck Center for Molecular MedicineBerlin, Germany; Department of Biophysics, Federal University of São PauloSão Paulo, Brazil.
authors.forename: Alessander O
authors.initials: AO
authors.lastname: Guimaraes
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Lataro
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Prado
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: de Oliveira
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Sarai C O
authors.initials: SC
authors.lastname: Candido
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Paloma
authors.initials: P
authors.lastname: Pais
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Mauricio S
authors.initials: MS
authors.lastname: Ribeiro
authors.affiliation: Max Delbruck Center for Molecular MedicineBerlin, Germany; Berlin Institute of Health, Charité-University Medicine BerlinBerlin, Germany; German Center for Cardiovascular Research, Partner Site BerlinBerlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Department of Biophysics, Federal University of São Paulo São Paulo, Brazil.
authors.forename: Joao B
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Maria C O
authors.initials: MC
authors.lastname: Salgado
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Helio C
authors.initials: HC
authors.lastname: Salgado
keywords: analysis spectral; angiotensina II; elastase-2; knockout mice; sympathovagal balance