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1 ICBM, Programa de Fisiopatología, Universidad de Chile, Facultad de Medicina, Santiago, Chile; International Center for Andean Studies (INCAS), Universidad de Chile, Santiago, Chile
2 ICBM, Programa de Fisiopatología, Universidad de Chile, Facultad de Medicina, Santiago, Chile
3 Departamento de Bioquímica y Biología Molecular, Universidad de Chile, Facultad de Ciencias Químicas y Farmacéuticas, Santiago, Chile
4 OB/GYN and Reproductive Science, University of California, San Francisco, San Francisco, California, United States
5 Facultad de Medicina, Pontificia Universidad Católica Madre y Maestra, Santiago de los Caballeros, Dominican Republic
6 Department of Physiology, University of Cambridge, Cambridge, United Kingdom
7 Department of Pediatrics, Academic Hospital Maastricht, University of Maastricht, Netherlands
8 Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, United Kingdom
9 ICBM, Programa de Fisiopatología, Universidad de Chile, Facultad de Medicina, Santiago, Chile; International Center for Andean Studies (INCAS), Universidad de Chile, Santiago, Chile; Universidad de Tarapacá and Centro de Investigaciones del Hombre en el Desierto, Arica, Chile
* To whom correspondence should be addressed. E-mail: allanos{at}med.uchile.cl.
Perinatal exposure to chronic hypoxia induces sustained pulmonary hypertension and structural and functional changes in both, pulmonary and systemic vascular beds. The aim of this study was to analyze the consequences of high altitude chronic hypoxia during gestation and after birth in pulmonary and femoral vascular responses in newborn sheep. Lowland (LLNB, 580m) and highland (HLNB, 3,600m) newborn lambs were cathetherized under general anesthesia and submitted to acute sustained or stepwise hypoxic episodes. Contractile and dilator responses of isolated pulmonary and femoral small arteries were analyzed in a wire myograph. Under basal conditions, HLNB had a higher pulmonary arterial pressure (PAP, 20.2+2.4 vs 13.6+0.5 mmHg, p<0.05) and cardiac output (CO, 342+23 vs 279+13 ml.min-1.kg-1, p<0.05) compared to LLNB. In small pulmonary arteries, HLNB showed a greater contractile capacity and a higher sensitivity to nitric oxide. In small femoral arteries, HLNB had a lower maximal contraction than LLNB with a higher maximal response and sensitivity to noradrenaline and phenylephrine. In acute superimposed hypoxia, HLNB reached a higher PAP and FVR than LLNB. Graded hypoxia showed that average PAP was always higher in HLNB compared to LLNB at any PO2. Newborn lambs from pregnancies at altitude have stronger pulmonary vascular responses to acute hypoxia associated with higher arterial contractile status. In addition, the systemic vascular response to acute hypoxia is increased in high altitude newborns, associated with higher arterial adrenergic responses. These responses determined in intrauterine life and early after birth could be adaptive to the chronic hypoxia in the Andean altiplano.
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