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Am J Physiol Heart Circ Physiol (February 4, 2005). doi:10.1152/ajpheart.00812.2004
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Submitted on August 9, 2004
Accepted on February 1, 2005

Heart mitochondrial nitric oxide synthase is up-regulated in male rats exposed to high altitude (4340 m)

Gustavo F Gonzales1, Francisco A Chung1, Sara Miranda1, Laura B Valdez2, Tamara Zaobornyj2, Juanita Bustamante2, and Alberto Boveris2*

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

* To whom correspondence should be addressed. E-mail: aboveris{at}ffyb.uba.ar.

Male rats exposed for 21 days to high altitude (4340 m) responded with arrest of gain weight and increased hematocrit and testosterone levels. High altitude significantly (58%) increased heart mitochondrial nitric oxide synthase (mtNOS) activity, whereas heart cytosolic eNOS and liver mtNOS were not affected. Western blot analysis found heart mitochondria reacting only with anti-iNOS antibodies, whereas the post mitochondrial fraction reacted with anti-iNOs and anti-eNOS antibodies. In vitro measured NOS activities allowed the estimation of cardiomyocite capacity for NO production, a value that increased from 57 (sea level) to 79 nmol NO/min.g heart (4340 m). The contribution of mtNOS to total cell NO production increased from 62 % (sea level) to 71 % (4340 m). Heart mtNOS activity showed a linear relationship with hematocrit and a biphasic quadratic association with estradiol and testosterone. Multivariate analysis showed that exposure to high altitude linearly associates with hematocrit and heart mtNOS activity, and that testosterone/estradiol ratio and heart weight were not linearly associated with mtNOS activity. We conclude that high altitude triggers a physiological adaptive response that up-regulates heart mtNOS activity and is associated, in an opposed manner, with the serum levels of testosterone and estradiol.




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