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Title: Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice
Authors: Becari, Christiane
Durand, Marina T.
Guimaraes, Alessander O. [UNIFESP]
Lataro, Renata M.
Prado, Cibele M.
de Oliveira, Mauro
Candido, Sarai C. O.
Pais, Paloma
Ribeiro, Mauricio S.
Bader, Michael
Pesquero, Joao B. [UNIFESP]
Salgado, Maria C. O.
Salgado, Helio C.
Keywords: elastase-2
angiotensina II
sympathovagal balance
analysis spectral
knockout mice
Issue Date: 2017
Publisher: Frontiers Media Sa
Citation: Frontiers In Physiology. Lausanne, v. 8, p. -, 2017.
Abstract: In vitro and ex vivo experiments 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-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2K0) 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-2K0 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 WI) in ELA-2K0 mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2K0 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-2K0 mice.
ISSN: 1664-042X
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