Long-lasting cardiovascular responses to gestation at high altitude: lessons from a sheep model

Abstract

Adaptations of maternal and fetal cardiovascular physiology may be most important when there are unfavourable environmental conditions during pregnancy, such as hypoxia when living at high altitudes. Chronic hypobaric hypoxia during intrauterine development may permanently modify fetal organ function, conditioning an increased risk for cardiovascular adult diseases. This review summarizes our 20 years of work on a sheep model assessing the impact of high-altitude hypoxia on the offspring's cardiovascular development and function at fetal, neonatal and adult stages. We further discuss diverse experimental approaches to describe the involved mechanisms in the systemic and pulmonary circulation, such as the pulmonary hypoxic vasoconstriction, the roles of nitric oxide, carbon monoxide and oxidative stress in short- and long-lasting consequences. Research on high-altitude sheep models lays the groundwork for further studies into how hypoxic conditions during development impact long-term cardiovascular health and the potential therapeutic approaches, with promising findings pertinent for human health at highlands.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.

Keywords: cardiovascular development; cardiovascular programming; chronic hypoxia; developmental origins of health and disease; fetal cardiovascular physiology; melatonin; oxidative stress.