High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep

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 consequences of high-altitude chronic hypoxia during gestation and early after birth in pulmonary and femoral vascular responses in newborn sheep. Lowland (LLNB; 580 m) and highland (HLNB; 3,600 m) 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 (342 +/- 23 vs. 279 +/- 13 ml(.)mm(-1.)kg(-1), P < 0.05) compared with LLNB. In small pulmonary arteries, HLNI3 showed greater contractile capacity and higher sensitivity to nitric oxide. In small femoral arteries, FlLNB had lower maximal contraction than LLNI3 with higher maximal response and sensitivity to noradrenaline and phenylephrine. In acute superimposed hypoxia, HLNB reached higher PAP and femoral vascular resistance than LLNB. Graded hypoxia showed that average PAP was always higher in HLNB compared with LLNB at any Po-2. Newborn lambs from pregnancies at high altitude have stronger pulmonary vascular responses to acute hypoxia associated with higher arterial contractile status. In addition, systentic vascular response to acute hypoxia is increased in high-altitude newborns, associated with higher arterial adrenergic responses. These responses deterritined in intrauterine life and early after birth could be adaptive to chronic hypoxia in the Andean altiplano.This work was funded by the National Fund for Scientific and Technological Development, Chile (FONDECYT), Grant 1050479, The Wellcome Trust Collaborative Research Initiative, United Kingdom, Grant 072256, and the Latin America Academic Training, European Union, Program ALFA Project Grant II-0379-FCD. Emilio Herrera is a Fellow of Programme for Increasing Education Quality and Equity (MECESUP), Chile, Grant UCh0115 and the Beca University of Chile Grant PG/54/2005. Mark Hanson is supported by the British Heart Foundation