Mitochondria are implicated in rat heart adaptation to chronic hypoxia

ZAOBORNYJ T; VALDEZ LB; COSTA LE; GONZALES GF; BOVERIS A

Davos, Switzerland

Congreso; XIII Biennial Meeting of the society for Free Radical Research International; 2006

Society for Free Radical Research International

This study analyzes heart adaptation to chronic hypobaric hypoxia focusing on classical physiological markers along with mitochondrial parameters, in particular, mtNOS activity and expression. Rats were submitted to (a) simulated (hypobaric chamber, 5000 m, 53.8 kPa, 18 mo); or (b) natural (Cerro de Pasco, Perú, 4340 m, 61.3 kPa, 84 d) high altitude hypoxia. Control animals were maintained at about sea level. (a) Adapted rats showed 20-60% increased mtNOS activity, a retardation of decline in papillary muscle contractility upon aging and an improved recovery after anoxia-reoxygenation. Complex I-III and IV activities decreased by 36% and 12% with age, but were not affected by hypoxia. (b) Adapted animals exhibited gain weight arrest, right ventricle hypertrophy (128%, t½=26 d) and increased hematocrit (40%, t½=11 d). Heart mtNOS activity and expression resulted 70% (t½=19 d) and  60% enhanced while cytosolic NOS resulted unchanged. There was a linear relationship between hematocrit and heart mtNOS activity (R2=0.88, P £ 0.05). Exposure modified mtNOS contribution to total cellular NO production (from 86% to 96%). Complex I-III activity was increased by 15% but Complex II-III and IV activities were not affected by exposure. We conclude that chronic hypoxia triggers a response in which mtNOS up-regulation is implicated.