title: High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep.
abstract: 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 x min(-1) x kg(-1), P < 0.05) compared with LLNB. In small pulmonary arteries, HLNB showed greater contractile capacity and higher sensitivity to nitric oxide. In small femoral arteries, HLNB had lower maximal contraction than LLNB 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 Po2. Newborn lambs from pregnancies at high altitude have stronger pulmonary vascular responses to acute hypoxia associated with higher arterial contractile status. In addition, 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 chronic hypoxia in the Andean altiplano.
authors.affiliation: Laboratorio de Fisiología y Fisiopatología del Desarrollo, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Pulgar
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Riquelme
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Sanhueza
authors.forename: Roberto V
authors.initials: RV
authors.lastname: Reyes
authors.forename: Germán
authors.initials: G
authors.lastname: Ebensperger
authors.forename: Julian T
authors.initials: JT
authors.lastname: Parer
authors.forename: Enrique A
authors.initials: EA
authors.lastname: Valdéz
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Blanco
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Aníbal J
authors.initials: AJ
authors.lastname: Llanos
mesh_terms: D000222:Adaptation, Physiological; D000531:Altitude; D000532:Altitude Sickness / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output; D002908:Chronic Disease; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D010101:Oxygen Consumption; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange; D012756:Sheep