Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude. Effect of sildenafil, L-NAME and L-arginine.

ZAOBORNYJ T; VALDEZ LB; IGLESIAS DE; GASCO M,; GONZALES GF; BOVERIS A

Santiago, Chile

Congreso; Free Radicals and Antioxidants in Chile 2009: VI Meeting of the Society for Free Radical Biology and Medicine, South American Group; 2009

VI Meeting of the Society for Free Radical Biology and Medicine, South American Group

Rats submitted to high altitude (Cerro de Pasco, Perú, 4340 m, PO2=12.2 kPa) for up to 84 days showed a physiological adaptive response with decreased body weight gain (15%), increased right ventricle weight (100%) and increased hematocrit (40%), as compared with sea level animals. These classical parameters of adaptation to high altitude were accompanied by an increase in heart mitochondrial enzymes: complexes I-III activity by 34% and mtNOS activity and expression by more than 75%. The hyperbolic increase for mtNOS activity during adaptation to high altitude was similar to the observed pattern for hematocrit. Hematocrit and mtNOS activity mean values correlated linearly (R2 = 0.75, P £ 0.05). Chronic treatment for 28 days with sildenafil (50 mg/kg.day) decreased the response of mtNOS to high altitude by 25%. Conversely, L-NAME treatment (8.3 mg/kg.day) increased such response by 40%, whereas L-arginine treatment (106 mg/kg.day) had no effect. Nitric oxide production by mtNOS accounts for about 49% of total cellular NO production in sea level rats and for about 54% in rats exposed to high altitude for 84 days. It is concluded that mtNOS is a substantial source of cardiac NO, a factor in the adaptive response to sustained heart hypoxia which is susceptible to be modified by pharmacological treatments. Supported by PIP6320 (CONICET), PICT38326 (ANPCYT), B027 (UBA) and Vicerectorate of Investigation of the Universidad Peruana Cayetano Heredia (Peru).