INVOLVEMENT OF HEART MITOCHONDRIAL NITRIC OXIDE SYNTHASE AND TIME COURSE OF RAT ADAPTATION TO HIGH ALTITUDE

ZAOBORNYJ T; VALDEZ LB; GASCO M; GONZALES GF; BOVERIS A

Moscu, Russia

Congreso; 14th European Bioenergetics Conference; 2006

The present work analyzes the time course of the adaptive response to high altitude (Cerro de Pasco, Perú, 4,340 m) considering classical physiological parameters and mtNOS activity and expression. The hematocrit of rats exposed to high altitude showed a hyperbolic increase and were up to 40 % higher than those of sea level rats with a t½ of 11 days. Right ventricle weight was increased by 128 % after 84 days of exposure with a t½ of 26 days. Heart mtNOS activity showed an hyperbolic increase almost parallel to hematocrit with a t½ of 19 days. A linear relationship was found between hematocrit and heart mtNOS activity (R2=0.88, P £ 0.05). After 84 days of exposure, heart mtNOS activity was 70 % higher in high altitude than in sea level animals. The observed enhancement of mtNOS biochemical activity was accompanied by a 60 % increase in mtNOS expression recognized by anti-iNOS antibodies. This fact suggests a common signaling pathway leading to increased transcription of the genes encoding for erythropoietin and mtNOS. According to our results, we conclude that mtNOS and mitochondria are the main source of cardiomyocytes NO and constitute an important factor in the adaptive response to sustained heart hypoxia: mtNOS accounted for about 86 % of total cellular NO production in sea level rats and for about 96 % in rats exposed to high altitude for 84 days.