INVESTIGADORES
ENNIS Irene Lucia
congresos y reuniones científicas
Título:
AT1 Receptor Blockade with Losartan Prevents Maladaptive Hypertrophy in Pressure Overload by Inhibiting Ros Release
Autor/es:
CINGOLANI OH; PÉREZ NG; MOSCA SM; SCHINELLA GR; CÓNSOLE G ; ENNIS IL; ESCUDERO EM; CINGOLANI HE
Lugar:
Washington, DC
Reunión:
Congreso; High Blood Pressure Research; American heart Association; 2010
Resumen:
AT1
Receptor Blockade with Losartan Prevents Maladaptive Hypertrophy in
Pressure
Overload by Inhibiting Ros Release
Oscar H Cingolani, Johns Hopkins Univ, Baltimore, MD;
Nestor G Pe´ rez, Susana M Mosca, G
R Schinella, Cntr de Investigaciones Cardiovasculares.
Facultad de Medicina de La PLata,
La Plata, Argentina; G M Co´ nsole, Cntr de Investigaciones
Cardiovasculares. Facultad de
Medicina de La Plata., La Plata, Argentina; Irene L Ennis,
Eduardo Escudero, Horacio E
Cingolani; Cntr de Investigaciones Cardiovasculares.
Facultad de Medicina de La PLata,
La
Plata, Argentina
Pressure
overload hypertrophy (POH) has been traditionally viewed as a compensatory
response
that normalizes left ventricular (LV)
wall stress to compensate for increased afterload.
This controversial
concept implies that blunting POH without changing pressure would
therefore
decrease cardiac function. To challenge this view, transverse aortic
constriction (TAC)
was
performed in mice and maintained for 7 weeks. From the beginning, a group of
mice
received
the AT1 receptor blocker Losartan (TAC_LOS, 40 mg/Kg) in the drinking water,
whereas a
second group did not (TAC). LV
pressure did not change between groups. Cardiac
function
was assessed at the end by echocardiography and pressure-volume loop analysis.
Mice
subjected to TAC had an increase in LV
mass of _80%
compared to sham. LOS prevented
POH
(table) and showed increased cardiac contractility when compared to TAC (p_0.05 for LV
ejection
fraction and preload recruitable stroke work) despite less LV hypertrophy. Increased LV
collagen
volume fraction was observed in the TAC group; and was significantly reduced by
LOS
(P _0.05).
Cardiac levels of p-90RSK, a PKC downstream effector involved in ROS
modulation,
increased
by 39% in TAC and was normalized with LOS (p _0.05). Lipid peroxidation
(plasma
TBARS)
was elevated in TAC, and blunted in TAC_LOS (P _0.05). We
conclude that in mice,
cardiac
POH seems to be a maladaptive phenomenon in which reactive oxygen species
appear
to play
an important role. LOS seems to prevent this maladaptive hypertrophy and
maintain
contractility
in spite of a higher workload. These effects could be mediated, at least in
part
through a
redox sensitive effect involving P-90 RSK.