Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide

JOSE MILEI; ANALIA CZERNICZYNIEC; LIDIA E.COSTA; BARBARA PIOTRKOWSKI; PABLO H.LA PADULA; LIDIA E.COSTA; BARBARA PIOTRKOWSKI; PABLO H.LA PADULA; SILVIA LORESARNAIZ; MELISA ETCHEGOYEN; SILVIA LORESARNAIZ; MELISA ETCHEGOYEN; JOSE MILEI; ANALIA CZERNICZYNIEC

NITRIC OXIDE-BIOLOGY AND CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

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

1089-8603

AimIn 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.MethodsRats 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.ResultsCytosolic 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 was reversed 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 L-arg papillary muscles of hypoxic rats.ConclusionExposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.