Chu Alison, Gozal David, Cortese Rene, Wang Yang
Department of Pediatrics, University of Chicago, Chicago, Illinois.
Pediatr Res. 2015 Mar;77(3):425-33. doi: 10.1038/pr.2014.197. Epub 2014 Dec 17.
Ex-premature infants are at higher risk for hypertension and cardiovascular disease as adults, although the mechanisms underlying such increased risks are unknown. We hypothesize that postnatal exposure to intermittent hypoxia (IH) leads to cardiovascular dysfunction in adulthood with alterations of the renin-angiotensin pathway.
Neonatal mice were exposed to IH for 4 wk. At the age of 3 mo, various cardiovascular measurements were obtained.
IH-exposed mice exhibited higher systolic blood pressure, impaired baroreflex responses, and decreased heart rate variability. Furthermore, IH-exposed mice manifested evidence of endothelial dysfunction, as shown by reduced reperfusion indices after tail vessel occlusion and impaired vasodilatory responses to acetylcholine. CD31(+) endothelial cells isolated from mesenteric arteries of IH-exposed mice expressed higher levels of angiotensin-converting enzyme and reactive oxygen species; plasma angiotensin-II levels were also significantly higher in these animals. In addition, DNA methylation patterns of the Ace1 and the Agt genes in these cells were congruent with their expression patterns.
Our results suggest that exposures to postnatal IH alter the normal development of the renin-angiotensin system and promote the occurrence of cardiovascular dysfunction during adulthood in mice.
早产婴儿成年后患高血压和心血管疾病的风险更高，尽管这种风险增加的潜在机制尚不清楚。我们推测，出生后暴露于间歇性缺氧（IH）会导致成年期心血管功能障碍，并伴有肾素-血管紧张素途径的改变。
将新生小鼠暴露于间歇性缺氧环境4周。在3个月大时，进行各种心血管测量。
暴露于间歇性缺氧的小鼠表现出更高的收缩压、压力反射反应受损和心率变异性降低。此外，暴露于间歇性缺氧的小鼠表现出内皮功能障碍的迹象，如尾部血管闭塞后再灌注指数降低以及对乙酰胆碱的血管舒张反应受损。从暴露于间歇性缺氧的小鼠肠系膜动脉分离出的CD31(+)内皮细胞表达更高水平的血管紧张素转换酶和活性氧；这些动物的血浆血管紧张素II水平也显著更高。此外，这些细胞中Ace1和Agt基因的DNA甲基化模式与其表达模式一致。
我们的结果表明，出生后暴露于间歇性缺氧会改变肾素-血管紧张素系统的正常发育，并促进小鼠成年期心血管功能障碍的发生。
