Heart adaptation to environmental hypoxia. Up-regulation of mitochondrial nitric oxide synthase.

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

Alba, Italia

Congreso; Joint Meeting of the Oxygen Club of California and the University of Torino, Oxidants and Antioxidants in Biology.; 2005

Oxygen Club of California

The present study determines the time course and effect of chronic exposition to environmental hypoxia on heart mitochondrial NOS (mtNOS). The changes are considered along with other markers of adaptation such as hematocrit, heart contractility parameters and mitochondrial enzymatic activities. a) Hypoxia in hypobaric chamber: Rats were housed in a hypobaric chamber (53.8 kPa) and sacrificed at 2, 4, 8, 12 and 18 mo of age. Hypoxic rats showed 20-60% increased left ventricle mtNOS activity as compared with their normoxic siblings. Left ventricle NADH-cytochrome c reductase and cytochrome oxidase activities were not affected by hypoxia. The increase in mtNOS activity of hypoxic rats was associated to a retardation of the decline in the mechanical activity of papillary muscle upon aging and an improved recovery after anoxia-reoxygenation. b) Hypoxia at high altitude: Rats were transported to Cerro de Pasco, Perú (4340 m, 61.3 kPa) and sacrificed at 7, 14, 21, 42 and 84 days. Animals responded with arrest of gain weight, right ventricle hypertrophy (230%) and increased hematocrit (40%). High altitude increased (80%) heart mtNOS activity, whereas it did not affect heart cytosolic eNOS activity. There was an increase of 60% in the heart mitochondrial NOS expression. A linear correlation (r2 = 0.88) between hematocrit and mtNOS activity was observed. In conclusion, environmental hypoxia triggers an adaptive response that involves the up-regulation of heart mtNOS.