Heart mitochondrial nitric oxide in rat adaptation to high altitude (4340 m). Effect of sildenafil, L-NAME and L-arginine

ZAOBORNYJ T; VALDEZ LB; IGLESIAS D; GASCO M; GONZALES GF; BOVERIS A

Montevideo, Uruguay

Congreso; V Meeting of the South American Group of the Society for Free Radical Biology and Medicine; 2007

Society for Free Radical Biology and Medicine

  Previous work from our laboratory showed that exposure to high altitude (Cerro de Pasco, Perú, 4340 m) produced an increase in heart mtNOS activity and expression. The goal of this work was to evaluate if this phenomenon is affected by pharmacological treatment with sildenafil, L-NAME and L-arginine. The study comprised 8 groups: 4 groups of rats were mantained at sea level (Lima, 150 m; SL) and 4 other groups at Cerro de Pasco (4340 m; HA). Two groups were control (SL-C, HA-C), two groups were treated with sildenafil (50 mg/kg.day; SL-S and HA-S), two groups with L-NAME (8.3 mg/kg.day, SL-N and HA-N), and two with L-arginine (106 mg/kg.day; SL-A and HA-A). Every group of animals was mantained at controlled room temperature. Animals were weighted and sacrificed at 7, 14, 21 and 28 days; hearts were excised, weighted and used for isolation of mitochondria. None of the treatments modified significantly heart mtNOS activity of rats at SL, as compared with their SL-C. At 21 days of exposure,  mtNOS activity of HA-C was 150% higher than in SL-C. In turn, HA-A mtNOS activity was 20% higher than HA-C; HA-N and HA-S mtNOS activity were 12 and 49% lower than HA-C, respectively. All groups of animals exposed to high altitude responded with increased hematocrit (34% at 21 days). A linear relationship was found between hematocrit and heart mtNOS activity in all the groups of animals exposed to high altitude (R2=0.85, P £ 0.05). Treatment with sildenafil, L-NAME and L-arginine modified the physiological adaptive response in which the up-regulation of heart mtNOS activity is involved.