INVESTIGADORES
VALDEZ Laura Beatriz
congresos y reuniones científicas
Título:
Effect of L-NAME, L-arginine and Sildenafil on mitochondrial nitric oxide metabolism in rat heart adaptation to high altitude.
Autor/es:
ZAOBORNYJ T; VALDEZ LB; IGLESIAS DE,; GASCO M; GONZALES GF; BOVERIS A
Lugar:
Santa Bárbara, California
Reunión:
Congreso; Annual Meeting of Oxygen Club of California. 2008 World Congress: Oxidants & Antioxidants in Biology; 2008
Institución organizadora:
Oxygen Club of California
Resumen:
This work
studies heart mtNOS activity and expression in the adaptive response to
high altitude at Cerro de Pasco (Perú, 4,340m, PO2=12.2kPa) and
the effect of pharmacological treatments on that adaptation. Rats were
mantained at sea level (SL) and high altitude (HA); 2 groups were
control (SL-C, HA-C), 2 groups were treated with L-NAME (8.3 mg/kg.day,
SL-N and HA-N), 2 with L-arginine (106 mg/kg.day; SL-A and HA-A), and 2
with sildenafil (50 mg/kg.day; SL-S and HA-S). Animals were sacrificed
at 7, 14, 21, 28, 42 and 84 days. HA animals showed right
ventricle hypertrophy at 42 and 84 days. Heart mtNOS activity was 70%
higher in HA than in SL animals and neither of the treatments suppressed
this response. The increase in mtNOS activity was accompanied by an
increase of 60% in mtNOS expression. Heart mtNOS activity was about 150%
higher in SL-N than in SL-C, suggesting that sustained inhibition of
mtNOS results in an up-regulation of this enzyme. The combination of HA
and L-NAME produced a faster enhancement (10%) in mitochondrial NO
production than HA itself. Conversely, sildenafil treatment impaired
mtNOS activity response to HA (20%). All the groups maintained at HA
showed an hyperbolic response of hematocrit as a function of time of
exposure. The mean values of hematocrit and mtNOS activity from HA rats
correlated linearly (R2=0.82, P£0.05). We
conclude that mtNOS is a substantial source of cardiac NO and
constitutes a factor in the adaptive response to sustained heart
hypoxia, susceptible to be modified by pharmacological treatments.