Cardioprotection after acute exposure to simulated high altitude in rats.

LA PADULA, P.; ETCHEGOYEN, M.; CZERNICZYNIEC, A.; PIOTRKOWSKI, B.; LORES-ARNAIZ, S.; MILEI, J. ; COSTA, L.

NITRIC OXIDE-BIOLOGY AND CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2018 vol. 73 p. 52 - 59

1089-8603

Aim: In previous studies, upregulation of NOS during acclimatization of rats to sustained hypobaric hypoxia was associated to cardioprotection, evaluated as an increased tolerance of myocardium to hypoxia/reoxygenation.The objective of the present work was to investigate the effect of acute hypobaric hypoxia and the role of endogenous NO concerning cardiac tolerance to hypoxia/reoxygenation under β-adrenergic stimulation.Methods: Rats were submitted to 58.7 kPa in a hypopressure chamber for 48 h whereas their normoxic controls remained at 101.3 kPa. By adding NOS substrate L-arg, or blocker L-NNA, isometric mechanical activity of papillary muscles isolated from left ventricle was evaluated at maximal or minimal production of NO, respectively, under β-adrenergic stimulation by isoproterenol, followed by 60/30 min of hypoxia/reoxygenation.Activities of NOS and cytochrome oxidase were evaluated by spectrophotometric methods and expression of HIF1-α and NOS isoforms by western blot. Eosin and hematoxiline staining were used for histological studies.Results: Cytosolic expression of HIF1-α, nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats. Mitochondrial cytochrome oxidase activity was decreased by hypobaric hypoxia and this effect wasreversed by L-NNA. After H/R, recovery of developed tension in papillary muscles from normoxic rats was 51?60% (regardless NO modulation) while in hypobaric hypoxia was 70% ± 3 (L-arg) and 54% ± 1 (L-NNA).Other mechanical parameters showed similar results. Preserved histological architecture was observed only in Larg papillary muscles of hypoxic rats.Conclusion: Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.