Pablo H La Padula1, Melisa Etchegoyen2, Analia Czerniczyniec3, Barbara Piotrkowski4, Silvia Lores Arnaiz5, Jose Milei6, Lidia E Costa7. 1. Institute of Cardiological Research, School of Medicine, University of Buenos Aires, National Research Council of Argentina, 1122 Buenos Aires, Argentina. Electronic address: pablolapa@gmail.com. 2. Institute of Cardiological Research, School of Medicine, University of Buenos Aires, National Research Council of Argentina, 1122 Buenos Aires, Argentina. Electronic address: mberisso@gmail.com. 3. Institute of Biochemistry and Molecular Medicine (IBIMOL; UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, 1122 Buenos Aires, Argentina. Electronic address: anaczerni@gmail.com. 4. Institute of Biochemistry and Molecular Medicine (IBIMOL; UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, 1122 Buenos Aires, Argentina. Electronic address: barbara@ffyb.uba.ar. 5. Institute of Biochemistry and Molecular Medicine (IBIMOL; UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, 1122 Buenos Aires, Argentina. Electronic address: slarnaiz@ffyb.uba.ar. 6. Institute of Cardiological Research, School of Medicine, University of Buenos Aires, National Research Council of Argentina, 1122 Buenos Aires, Argentina. Electronic address: josemilei@gmail.com. 7. Institute of Cardiological Research, School of Medicine, University of Buenos Aires, National Research Council of Argentina, 1122 Buenos Aires, Argentina. Electronic address: lecosta@fmed.uba.ar.
Abstract
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 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. CONCLUSION: Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.
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 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. CONCLUSION: Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.
Authors: Robert T Mallet; Eugenia B Manukhina; Steven Shea Ruelas; James L Caffrey; H Fred Downey Journal: Am J Physiol Heart Circ Physiol Date: 2018-04-13 Impact factor: 4.733