Effects of hypoxia and aging on heart mtNOS

VALDEZ LB; ZAOBORNYJ T; ALVAREZ S; BOVERIS A,; LA-PADULA P; COSTA LE

Buenos Aires, Argentina

Congreso; XIIth Meeting of the Society for Free Radical Research International; 2004

Society for Free Radical Research International

This work studies the effects of chronic hypoxia and aging on heart mtNOS activity. The production of NO was measured by following spectrophotometrically the oxidation of oxyHb to metHb. The production of NO by heart mtNOS was 0.9±0.03 nmol NO/min.mg protein. Heart mtNOS seems to contribute with about 56% of the total cellular NO production. The state 4/state 3 transition regulates heart mtNOS activity and NO release in intact respiring mitochondria: NO production by heart mitochondria was 0.62±0.03 and 0.37±0.06 nmol NO/min.mg protein, in state 4 and 3 respectively. Heart mtNOS expression was selectively regulated by O2 availability in hypobaric conditions: the activity was 20-60% higher in hypoxic rats than in control animals depending on age. In contrast, NADH-cytochrome c reductase and cytochrome oxidase activities were not affected by hypoxia. The activity of rat heart mtNOS decreased with age: 20% from 12 to 72 wk of age. NADH-cytochrome c reductase and cytochrome oxidase activities were 38% and 5% reduced with aging. Thus, heart mtNOS is a highly regulated mitochondrial enzyme by physiological effectors, such as O2 availability; this enzyme, in turn, plays a regulatory role: mitochondrial [NO]ss levels modulate O2 uptake and O2- and H2O2 production rates. Nitric oxide and H2O2 constitute signals for metabolic control and are involved in the regulation of cellular processes, such as proliferation and apoptosis.