Effect of hypobaric hypoxia and aging on rat myocardium: modulation of mtNOS activity.

ZAOBORNYJ T; VALDEZ LB; LA PADULA P; COSTA LE; 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 aim of this work was to evaluate the effect of sustained hypobaric hypoxia and aging on heart mitochondrial NOS activity (mtNOS) along with other mitochondrial enzymes and to correlate mtNOS activity with parameters of papillary muscle contractility. Rats were chronically submitted to a simulated altitude of 5000 m (53.8 kPa) in an hypobaric chamber and sacrificed at 2, 4, 8, 12 and 18 mo of age. Heart mitochondria from young normoxic animals produced 0.62 and 0.37 nmol NO/min.mg protein in metabolic states 4 and 3, respectively. The mtNOS activity measured in submitochondrial membranes was 0.69 nmol NO/min.mg protein. Rats exposed to hypobaric hypoxia showed 20-60 % increased left ventricle mtNOS activity as compared with their normoxic siblings. Left ventricle NADH-cytochrome c reductase and cytochrome oxidase activities decreased by 36 % and 12 % from 2 to 18 mo of age, but were not affected by hypoxia. mtNOS up-regulation in hypoxia was associated with a retardation of the decline in the mechanical activity of papillary muscle upon aging and an improved recovery after anoxia-reoxygenation. Heart mtNOS activity is regulated by O2 in the inspired air and seems to play a role in NO-mediated signaling and myocardial contractility.