Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. II. mtNOS activity

• Published in: Journal of applied physiology (1985) 2005-06, Vol.98 (6), p.2370-2375
• Main Authors: Zaobornyj, Tamara, Valdez, Laura B, La Padula, Pablo, Costa, Lidia E, Boveris, Alberto
• Format: Article
• Language: English
• Subjects: Acclimatization - physiology; Aging; Aging - metabolism; Aging - pathology; Altitude; Animals; Cell Hypoxia - physiology; Cytochromes - metabolism; Heart; Heart Ventricles - enzymology; Male; Mechanotransduction, Cellular - physiology; Mitochondria - metabolism; Mitochondrial DNA; Myocardial Contraction - physiology; Nitric oxide; Nitric Oxide Synthase - metabolism; Organ Size - physiology; Papillary Muscles - cytology; Papillary Muscles - physiology; Pressure; Rats; Rats, Wistar; Rodents; Stress, Mechanical; Survival
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00986.2004

1 Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, and 2 Institute for Cardiological Research, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Submitted 7 September 2004 ; accepted in final form 3 February 2005 Mitochondrial nitric oxide (NO) production was assayed in rats submitted to hypobaric hypoxia and in normoxic controls (53.8 and 101.3 kPa air pressure, respectively). Heart mitochondria from young normoxic animals produced 0.62 and 0.37 nmol NO·min –1 ·mg protein –1 in metabolic states 4 and 3, respectively. This production accounts for a release to the cytosol of 29 nmol NO·min –1 ·g heart –1 and for 55% of the NO generation. The mitochondrial NO synthase (mtNOS) activity measured in submitochondrial membranes at pH 7.4 was 0.69 nmol NO·min –1 ·mg protein –1 . Rats exposed to hypobaric hypoxia for 2–18 mo showed 20–60% increased left ventricle mtNOS activity compared with their normoxic siblings. Left ventricle NADH-cytochrome- c reductase and cytochrome oxidase activities decreased by 36 and 12%, respectively, from 2 to 18 mo of age, but they were not affected by hypoxia. mtNOS upregulation in hypoxia was associated with a retardation of the decline in the mechanical activity of papillary muscle upon aging and an improved recovery after anoxia-reoxygenation. The correlation of left ventricle mtNOS activity with papillary muscle contractility (determined as developed tension, maximal rates of contraction and relaxation) showed an optimal mtNOS activity (0.69 nmol·min –1 ·mg protein –1 ). Heart mtNOS activity is regulated by O 2 in the inspired air and seems to play a role in NO-mediated signaling and myocardial contractility. mitochondrial nitric oxide; heart contractility; acclimatization Address for reprint requests and other correspondence: T. Zaobornyj, Fisicoquímica, Facultad de Farmacia y Bioquímica,, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina (E-mail: tamaraz{at}ffyb.uba.ar )