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

Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments. Am J Physiol Heart Circ Physiol 296: H1741–H1747, 2009. First published April 3, 2009; doi:10.1152/ajpheart.00422.2008.—Rats submitted to high altitude (Cerro...

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Detalles Bibliográficos
Autores: Zaobornyj, Tamara, Valdez, Laura Batriz, Iglesias, Dario Ezequiel, Gasco, Manuel, Gonzales, Gustavo F., Boveris, Alberto Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/102551
Acceso en línea:http://hdl.handle.net/11336/102551
Access Level:acceso abierto
Palabra clave:mtNOS ACTIVITY
mtNOS EXPRESSION
MITOCHONDRIAL RESPIRATORY COMPLEXES
HEMATOCRIT
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments. Am J Physiol Heart Circ Physiol 296: H1741–H1747, 2009. First published April 3, 2009; doi:10.1152/ajpheart.00422.2008.—Rats submitted to high altitude (Cerro de Pasco, Peru´, 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 kg1 day1 ) decreased the response of mtNOS to high altitude by 25%. Conversely, NGnitro-L-arginine methyl ester treatment (8.3 mg kg1 day1 ) increased such response by 40%, whereas L-arginine treatment (106 mg kg1 day1 ) 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.