Heart mitochondrial nitric oxide synthase is upregulated in male rats exposed to high altitude (4,340 m).
Male rats exposed for 21 days to high altitude (4,340 m) responded with arrest of weight gain and increased hematocrit and testosterone levels. High altitude significantly (58%) increased heart mitochondrial nitric oxide (NO) synthase (mtNOS) activity, whereas heart cytosolic endothelial NOS (eNOS) and liver mtNOS were not affected. Western blot analysis found heart mitochondria reacting only with anti-inducible NOS (iNOS) antibodies, whereas the postmitochondrial fraction reacted with anti-iNOS and anti-eNOS antibodies. In vitro-measured NOS activities allowed the estimation of cardiomyocyte capacity for NO production, a value that increased from 57% (sea level) to 79 nmol NO.min(-1).g heart(-1) (4,340 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-to-estradiol ratio and heart weight were not linearly associated with mtNOS activity. We conclude that high altitude triggers a physiological adaptive response that upregulates heart mtNOS activity and is associated in an opposed manner with the serum levels of testosterone and estradiol.
Gonzales
Gustavo F
GF
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
Chung
Francisco A
FA
Miranda
Sara
S
Valdez
Laura B
LB
Zaobornyj
Tamara
T
Bustamante
Juanita
J
Boveris
Alberto
A
D000531:Altitude; D000818:Animals; D001835:Body Weight; D004958:Estradiol / Q000097:blood; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013367:Submitochondrial Particles / Q000201:enzymology
D004958:Estradiol; D019001:Nitric Oxide Synthase