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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/H1741    most recent 00422.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Zaobornyj, T. Articles by Boveris, A. PubMed PubMed Citation Articles by Zaobornyj, T. Articles by Boveris, A.

Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments

¹Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina; and ²Facultad de Ciencias y Filosofía, Departamento de Ciencias Biológicas y Fisiológicas, Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia, Lima, Peru

Submitted 22 April 2008 ; accepted in final form 1 April 2009

Rats submitted to high altitude (Cerro de Pasco, Perú, 4,340 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%) 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 mitochondrial nitric oxide synthase (mtNOS) activity and expression by >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^–1·day^–1) decreased the response of mtNOS to high altitude by 25%. Conversely, N^G-nitro-L-arginine methyl ester treatment (8.3 mg·kg^–1·day^–1) increased such response by 40%, whereas L-arginine treatment (106 mg·kg^–1·day^–1) had no effect. Nitric oxide (NO) production by mtNOS accounts for 49% of total cellular NO production in sea level rats and for 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 that is susceptible to be modified by pharmacological treatments.

mitochondrial nitric oxide synthase activity; mitochondrial nitric oxide synthase expression; mitochondrial respiratory complexes; hematocrit; nitro-L-arginine methyl ester

This article has been cited by other articles:

				J. Nagendran and E. D. Michelakis Mitochondrial NOS is upregulated in the hypoxic heart: implications for the function of the hypertrophied right ventricle Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1723 - H1726. [Full Text] [PDF]