Herrera Emilio A, Pulgar Víctor M, Riquelme Raquel A, Sanhueza Emilia M, Reyes Roberto V, Ebensperger Germán, Parer Julian T, Valdéz Enrique A, Giussani Dino A, Blanco Carlos E, Hanson Mark A, Llanos Aníbal J
Laboratorio de Fisiología y Fisiopatología del Desarrollo, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Am J Physiol Regul Integr Comp Physiol. 2007 Jun;292(6):R2234-40. doi: 10.1152/ajpregu.00909.2006. Epub 2007 Feb 22.
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.
围产期暴露于慢性缺氧会导致持续性肺动脉高压以及肺血管床和体循环血管床的结构与功能改变。本研究的目的是分析妊娠期间及出生后早期高原慢性缺氧对新生绵羊肺血管和股血管反应的影响。在全身麻醉下对低地（LLNB；海拔580米）和高地（HLNB；海拔3600米）新生羔羊进行插管，并使其经历急性持续性或逐步性缺氧发作。在血管张力测定仪中分析离体肺小动脉和股小动脉的收缩和舒张反应。在基础条件下，与LLNB相比，HLNB的肺动脉压（PAP；20.2±2.4 vs. 13.6±0.5 mmHg，P<0.05）和心输出量（342±23 vs. 279±13 ml·min⁻¹·kg⁻¹，P<0.05）更高。在肺小动脉中，HLNB表现出更大的收缩能力和对一氧化氮更高的敏感性。在股小动脉中，HLNB的最大收缩低于LLNB，但对去甲肾上腺素和苯肾上腺素的最大反应和敏感性更高。在急性叠加缺氧时，HLNB的PAP和股血管阻力比LLNB更高。分级缺氧显示，在任何氧分压下，HLNB的平均PAP始终高于LLNB。来自高原妊娠的新生羔羊对急性缺氧的肺血管反应更强，同时动脉收缩状态更高。此外，高原新生羊对急性缺氧的体循环血管反应增强，与更高的动脉肾上腺素能反应相关。这些在子宫内生活和出生后早期确定的反应可能是对安第斯高原慢性缺氧的适应性反应。
