IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
artículos
Título:
Mitochondrial NO metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME and L-arginine treatments
Autor/es:
ZAOBORNYJ T; VALDEZ LB; IGLESIAS DE; GASCO M; GONZALES GF; BOVERIS A
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Año: 2009 vol. 296 p. 1741 - 1747
ISSN:
0363-6135
Resumen:
Rats submitted to high altitude (Cerro de Pasco, Perú, 4,340 m, Po(2) =
12.2 kPa) for up to 84 days showed a physiological adaptive response
with decreased body weight gain (15%), increased right ventricle weight
(100%), and increased hematocrit (40%) compared with sea level animals.
These classical parameters of adaptation to high altitude were
accompanied by an increase in heart mitochondrial enzymes: complexes
I-III activity by 34% and mitochondrial nitric oxide synthase (mtNOS)
activity and expression by >75%. The hyperbolic increase for mtNOS
activity during adaptation to high altitude was similar to the observed
pattern for hematocrit. Hematocrit and mtNOS activity mean values
correlated linearly (r(2) = 0.75, P <or= 0.05). Chronic treatment for
28 days with sildenafil (50 mg*kg(-1).day(-1)) decreased the response
of mtNOS to high altitude by 25%. Conversely, N(G)-nitro-l-arginine
methyl ester treatment (8.3 mg*kg(-1)*day(-1)) increased such response
by 40%, whereas l-arginine treatment (106 mg*kg(-1)*day(-1)) had no
effect. Nitric oxide (NO) production by mtNOS accounts for approximately
49% of total cellular NO production in sea level rats and for
approximately 54% in rats exposed to high altitude for 84 days. It is
concluded that mtNOS is a substantial source of cardiac NO, a factor in
the adaptive response to sustained heart hypoxia that is susceptible to
be modified by pharmacological treatments.