Heart mitochondrial nitric oxide synthase is up-regulated in rats exposed to high altitude (4340 m).

VALDEZ LB; ZAOBORNYJ T; GONZALES GF; BOVERIS A

Aguas de Lindoia, San Pablo, Brasil.

Congreso; IV Meeting of th South American Group of the Society for Free Radical Biology and Medicine.; 2005

South American Group of the Society for Free Radical Biology and Medicine.

The present study has been designed to determine the mitochondrial nitric oxide synthase activity (mtNOS) in rat heart and liver after exposure to high altitude along with other mitochondrial enzymatic activities; and to correlate these changes with other markers of adaptation. Rats were maintained at sea level (Lima, Perú, 150 m) or transported to Cerro de Pasco (Perú, 4340 m) and sacrificed at 7, 14, 21, 42 and 84 days. Animals exposed to high altitude responded with arrest of gain weight, right ventricle hypertrophy (up to 92%) and increased hematocrit (up to 55%). High altitude significantly increased heart mtNOS activity (up to 95%), whereas heart cytosolic eNOS and liver mtNOS were not affected. Western blot analysis found heart mitochondria reacting only with anti-iNOS antibodies, whereas the post mitochondrial fraction reacted with anti-iNOS and anti-eNOS antibodies. NADH-cytochrome c reductase activity as well as cytochrome aa3 and c contents were increased by 20-30% after 84 days of exposure to high altitude. Succinate-cytochrome c reductase activity was not affected by hypoxia. We conclude that high altitude triggers a physiological adaptive response in which the up-regulation of heart mtNOS activity is involved.